Differential Expression of Serum MicroRNAs Supports CD4⁺ T Cell Differentiation into Th2/Th17 Cells in Severe Equine Asthma.
Abstract: MicroRNAs (miRNAs) regulate post-transcriptional gene expression and may be exported from cells via exosomes or in partnership with RNA-binding proteins. MiRNAs in body fluids can act in a hormone-like manner and play important roles in disease initiation and progression. Hence, miRNAs are promising candidates as biomarkers. To identify serum miRNA biomarkers in the equine model of asthma we investigated small RNA derived from the serum of 34 control and 37 asthmatic horses. These samples were used for next generation sequencing, novel miRNA identification and differential miRNA expression analysis. We identified 11 significantly differentially expressed miRNAs between case and control horses: eca-miR-128, eca-miR-744, eca-miR-197, eca-miR-103, eca-miR-107a, eca-miR-30d, eca-miR-140-3p, eca-miR-7, eca-miR-361-3p, eca-miR-148b-3p and eca-miR-215. Pathway enrichment using experimentally validated target genes of the human homologous miRNAs showed a significant enrichment in the regulation of epithelial-to-mesenchymal transition (key player in airway remodeling in asthma) and the phosphatidylinositol (3,4,5)-triphosphate (PIP3) signaling pathway (modulator of CD4⁺ T cell maturation and function). Downregulated miR-128 and miR-744 supports a Th2/Th17 type immune response in severe equine asthma.
Publication Date: 2017-12-12 PubMed ID: 29231896PubMed Central: PMC5748701DOI: 10.3390/genes8120383Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research studied the use of microRNAs (miRNAs) found in horse serum as potential biomarkers for severe equine asthma. Scientists found that 11 specific miRNAs were significantly differently expressed in asthmatic versus control horses, pointing to potential impacts on biological pathways related to airway remodeling and T cell maturation and function.
Overall Research Context
- MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level. These molecules can be transported out of cells through exosomes or by associating with RNA-binding proteins.
- miRNAs in fluids within the body can behave in a similar way to hormones and can have crucial roles in the start and progression of diseases. Therefore, miRNAs present promising potential as disease biomarkers.
- The researchers’ goal was to identify specific miRNAs in horse serum that could serve as biomarkers for severe equine asthma.
Methodology
- Researchers conducted next-generation sequencing on small RNA derived from serum of 34 control horses and 37 horses suffering from asthma to identify novel miRNAs and evaluate the differential expression of miRNAs.
- Identified miRNAs sequences were then compared between asthmatic and non-asthmatic horses.
Findings
- The researchers identified 11 miRNAs (eca-miR-128, eca-miR-744, etc.) that showed significant differential expression between the two groups of horses.
- When the researchers examined pathway enrichment, using experimentally validated target genes of human equivalents of these miRNAs, they found a significant association with the regulation of epithelial-to-mesenchymal transition, which is a key part of airway remodeling in asthma, and phosphatidylinositol (3,4,5)-triphosphate (PIP3) signaling, which modifies CD4⁺ T cell maturation and function.
- They also noted that two specific miRNAs, miR-128 and miR-744, when downregulated, support a Th2/Th17 type immune response, which is typically present in severe equine asthma.
Implications
- The differential expression of these 11 miRNAs could potentially be used as biomarkers for severe equine asthma.
- This identify of these miRNAs and their roles in asthma provide new insight into the molecular mechanisms underlying severe asthma in horses, which could lead to new therapeutic strategies.
Cite This Article
APA
Pacholewska A, Kraft MF, Gerber V, Jagannathan V.
(2017).
Differential Expression of Serum MicroRNAs Supports CD4⁺ T Cell Differentiation into Th2/Th17 Cells in Severe Equine Asthma.
Genes (Basel), 8(12), 383.
https://doi.org/10.3390/genes8120383 Publication
Researcher Affiliations
- Department of Clinical Veterinary Medicine, Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Länggassstrasse 124, 3012 Bern, Switzerland. alicja@rth.dk.
- Department of Clinical Research and Veterinary Public Health, Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109A, 3012 Bern, Switzerland. alicja@rth.dk.
- Department of Clinical Veterinary Medicine, Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Länggassstrasse 124, 3012 Bern, Switzerland. matthias.kraft@vetsuisse.unibe.ch.
- Department of Clinical Research and Veterinary Public Health, Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109A, 3012 Bern, Switzerland. matthias.kraft@vetsuisse.unibe.ch.
- Department of Clinical Veterinary Medicine, Swiss Institute of Equine Medicine, Vetsuisse Faculty, University of Bern and Agroscope, Länggassstrasse 124, 3012 Bern, Switzerland. vinzenz.gerber@vetsuisse.unibe.ch.
- Department of Clinical Research and Veterinary Public Health, Institute of Genetics, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109A, 3012 Bern, Switzerland. vidhya.jagannathan@vetsuisse.unibe.ch.
Conflict of Interest Statement
The authors declare no conflict of interest.
References
This article includes 135 references
- Ansotegui I., Arruda L.K.P., Badellino H.A., Baena-Cagnani C.E., Bahna S.L., Baldacci S., Bel E., Bieber T.R.M., Bindslev-Jensen C., Blaiss M.S., et al. In: White Book on Allergy: Update 2013. Pawankar R., Holgate S.T., Canonica G.W., Lockey R.F., Blaiss M.S., editors. World Allergy Organization (WAO); Milwaukee, WI, USA: 2013.
- To T, Simatovic J, Zhu J, Feldman L, Dell SD, Lougheed MD, Licskai C, Gershon A. Asthma deaths in a large provincial health system. A 10-year population-based study.. Ann Am Thorac Soc 2014 Oct;11(8):1210-7.
- Gullach AJ, Risgaard B, Lynge TH, Jabbari R, Glinge C, Haunsø S, Backer V, Winkel BG, Tfelt-Hansen J. Sudden death in young persons with uncontrolled asthma--a nationwide cohort study in Denmark.. BMC Pulm Med 2015 Apr 14;15:35.
- Torgerson DG, Capurso D, Mathias RA, Graves PE, Hernandez RD, Beaty TH, Bleecker ER, Raby BA, Meyers DA, Barnes KC, Weiss ST, Martinez FD, Nicolae DL, Ober C. Resequencing candidate genes implicates rare variants in asthma susceptibility.. Am J Hum Genet 2012 Feb 10;90(2):273-81.
- Vercelli D. Discovering susceptibility genes for asthma and allergy.. Nat Rev Immunol 2008 Mar;8(3):169-82.
- Braun-Fahrländer C, Riedler J, Herz U, Eder W, Waser M, Grize L, Maisch S, Carr D, Gerlach F, Bufe A, Lauener RP, Schierl R, Renz H, Nowak D, von Mutius E. Environmental exposure to endotoxin and its relation to asthma in school-age children.. N Engl J Med 2002 Sep 19;347(12):869-77.
- Eisenbarth SC, Piggott DA, Huleatt JW, Visintin I, Herrick CA, Bottomly K. Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen.. J Exp Med 2002 Dec 16;196(12):1645-51.
- March ME, Sleiman PM, Hakonarson H. Genetic polymorphisms and associated susceptibility to asthma.. Int J Gen Med 2013;6:253-65.
- Wenzel SE. Asthma: defining of the persistent adult phenotypes.. Lancet 2006 Aug 26;368(9537):804-13.
- Ober C, Hoffjan S. Asthma genetics 2006: the long and winding road to gene discovery.. Genes Immun 2006 Mar;7(2):95-100.
- Moffatt MF, Kabesch M, Liang L, Dixon AL, Strachan D, Heath S, Depner M, von Berg A, Bufe A, Rietschel E, Heinzmann A, Simma B, Frischer T, Willis-Owen SA, Wong KC, Illig T, Vogelberg C, Weiland SK, von Mutius E, Abecasis GR, Farrall M, Gut IG, Lathrop GM, Cookson WO. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma.. Nature 2007 Jul 26;448(7152):470-3.
- Couëtil LL, Cardwell JM, Gerber V, Lavoie JP, Léguillette R, Richard EA. Inflammatory Airway Disease of Horses--Revised Consensus Statement.. J Vet Intern Med 2016 Mar-Apr;30(2):503-15.
- Bullone M, Lavoie JP. Asthma "of horses and men"--how can equine heaves help us better understand human asthma immunopathology and its functional consequences?. Mol Immunol 2015 Jul;66(1):97-105.
- Herszberg B, Ramos-Barbón D, Tamaoka M, Martin JG, Lavoie JP. Heaves, an asthma-like equine disease, involves airway smooth muscle remodeling.. J Allergy Clin Immunol 2006 Aug;118(2):382-8.
- Pirie RS, Dixon PM, McGorum BC. Evaluation of nebulised hay dust suspensions (HDS) for the diagnosis and investigation of heaves. 3: Effect of fractionation of HDS.. Equine Vet J 2002 Jul;34(4):343-7.
- Lanz S, Gerber V, Marti E, Rettmer H, Klukowska-Rötzler J, Gottstein B, Matthews JB, Pirie S, Hamza E. Effect of hay dust extract and cyathostomin antigen stimulation on cytokine expression by PBMC in horses with recurrent airway obstruction.. Vet Immunol Immunopathol 2013 Oct 1;155(4):229-37.
- Gerber V, Baleri D, Klukowska-Rötzler J, Swinburne JE, Dolf G. Mixed inheritance of equine recurrent airway obstruction.. J Vet Intern Med 2009 May-Jun;23(3):626-30.
- Swinburne JE, Bogle H, Klukowska-Rötzler J, Drögemüller M, Leeb T, Temperton E, Dolf G, Gerber V. A whole-genome scan for recurrent airway obstruction in Warmblood sport horses indicates two positional candidate regions.. Mamm Genome 2009 Aug;20(8):504-15.
- Marti E, Gerber H, Essich G, Oulehla J, Lazary S. The genetic basis of equine allergic diseases. 1. Chronic hypersensitivity bronchitis.. Equine Vet J 1991 Nov;23(6):457-60.
- Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, Li Q, Li X, Wang W, Zhang Y, Wang J, Jiang X, Xiang Y, Xu C, Zheng P, Zhang J, Li R, Zhang H, Shang X, Gong T, Ning G, Wang J, Zen K, Zhang J, Zhang CY. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases.. Cell Res 2008 Oct;18(10):997-1006.
- Hashimoto Y, Akiyama Y, Yuasa Y. Multiple-to-multiple relationships between microRNAs and target genes in gastric cancer.. PLoS One 2013;8(5):e62589.
- Li J, Zhang Y, Li D, Liu Y, Chu D, Jiang X, Hou D, Zen K, Zhang CY. Small non-coding RNAs transfer through mammalian placenta and directly regulate fetal gene expression.. Protein Cell 2015 Jun;6(6):391-396.
- Liang H, Gong F, Zhang S, Zhang CY, Zen K, Chen X. The origin, function, and diagnostic potential of extracellular microRNAs in human body fluids.. Wiley Interdiscip Rev RNA 2014 Mar-Apr;5(2):285-300.
- Eissa NT. The exosome in lung diseases: Message in a bottle.. J Allergy Clin Immunol 2013 Mar;131(3):904-5.
- Simpson LJ, Patel S, Bhakta NR, Choy DF, Brightbill HD, Ren X, Wang Y, Pua HH, Baumjohann D, Montoya MM, Panduro M, Remedios KA, Huang X, Fahy JV, Arron JR, Woodruff PG, Ansel KM. A microRNA upregulated in asthma airway T cells promotes TH2 cytokine production.. Nat Immunol 2014 Dec;15(12):1162-70.
- Sethi A, Kulkarni N, Sonar S, Lal G. Role of miRNAs in CD4 T cell plasticity during inflammation and tolerance.. Front Genet 2013;4:8.
- Okoye IS, Czieso S, Ktistaki E, Roderick K, Coomes SM, Pelly VS, Kannan Y, Perez-Lloret J, Zhao JL, Baltimore D, Langhorne J, Wilson MS. Transcriptomics identified a critical role for Th2 cell-intrinsic miR-155 in mediating allergy and antihelminth immunity.. Proc Natl Acad Sci U S A 2014 Jul 29;111(30):E3081-90.
- Kim MC, Lee SW, Ryu DY, Cui FJ, Bhak J, Kim Y. Identification and characterization of microRNAs in normal equine tissues by Next Generation Sequencing.. PLoS One 2014;9(4):e93662.
- Pacholewska A, Mach N, Mata X, Vaiman A, Schibler L, Barrey E, Gerber V. Novel equine tissue miRNAs and breed-related miRNA expressed in serum.. BMC Genomics 2016 Oct 26;17(1):831.
- Buza T, Arick M 2nd, Wang H, Peterson DG. Computational prediction of disease microRNAs in domestic animals.. BMC Res Notes 2014 Jun 27;7:403.
- van der Kolk JH, Pacholewska A, Gerber V. The role of microRNAs in equine medicine: a review.. Vet Q 2015 Jun;35(2):88-96.
- Kirschner MB, Edelman JJ, Kao SC, Vallely MP, van Zandwijk N, Reid G. The Impact of Hemolysis on Cell-Free microRNA Biomarkers.. Front Genet 2013;4:94.
- Pacholewska A, Jagannathan V, Drögemüller M, Klukowska-Rötzler J, Lanz S, Hamza E, Dermitzakis ET, Marti E, Leeb T, Gerber V. Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma.. PLoS One 2015;10(8):e0136103.
- Ramseyer A, Gaillard C, Burger D, Straub R, Jost U, Boog C, Marti E, Gerber V. Effects of genetic and environmental factors on chronic lower airway disease in horses.. J Vet Intern Med 2007 Jan-Feb;21(1):149-56.
- Laumen E, Doherr MG, Gerber V. Relationship of horse owner assessed respiratory signs index to characteristics of recurrent airway obstruction in two Warmblood families.. Equine Vet J 2010 Mar;42(2):142-8.
- Bosshard S, Gerber V. Evaluation of coughing and nasal discharge as early indicators for an increased risk to develop equine recurrent airway obstruction (RAO).. J Vet Intern Med 2014 Mar-Apr;28(2):618-23.
- Pacholewska A, Drögemüller M, Klukowska-Rötzler J, Lanz S, Hamza E, Dermitzakis ET, Marti E, Gerber V, Leeb T, Jagannathan V. The transcriptome of equine peripheral blood mononuclear cells.. PLoS One 2015;10(3):e0122011.
- Unger L, Fouché N, Leeb T, Gerber V, Pacholewska A. Optimized methods for extracting circulating small RNAs from long-term stored equine samples.. Acta Vet Scand 2016 Jun 29;58(1):44.
- Kirschner MB, Kao SC, Edelman JJ, Armstrong NJ, Vallely MP, van Zandwijk N, Reid G. Haemolysis during sample preparation alters microRNA content of plasma.. PLoS One 2011;6(9):e24145.
- Andrews S. FastQC—A Quality Control Tool for High Throughput Sequence Data. 2010.
- Martin M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet J 2011;17:10.
- European Nucleotide Archive. [(accessed on 24 April 2017)]; Available online: https://www.ebi.ac.uk/ena/data/view/PRJEB20494.
- Wade CM, Giulotto E, Sigurdsson S, Zoli M, Gnerre S, Imsland F, Lear TL, Adelson DL, Bailey E, Bellone RR, Blöcker H, Distl O, Edgar RC, Garber M, Leeb T, Mauceli E, MacLeod JN, Penedo MC, Raison JM, Sharpe T, Vogel J, Andersson L, Antczak DF, Biagi T, Binns MM, Chowdhary BP, Coleman SJ, Della Valle G, Fryc S, Guérin G, Hasegawa T, Hill EW, Jurka J, Kiialainen A, Lindgren G, Liu J, Magnani E, Mickelson JR, Murray J, Nergadze SG, Onofrio R, Pedroni S, Piras MF, Raudsepp T, Rocchi M, Røed KH, Ryder OA, Searle S, Skow L, Swinburne JE, Syvänen AC, Tozaki T, Valberg SJ, Vaudin M, White JR, Zody MC, Lander ES, Lindblad-Toh K. Genome sequence, comparative analysis, and population genetics of the domestic horse.. Science 2009 Nov 6;326(5954):865-7.
- Friedländer MR, Mackowiak SD, Li N, Chen W, Rajewsky N. miRDeep2 accurately identifies known and hundreds of novel microRNA genes in seven animal clades.. Nucleic Acids Res 2012 Jan;40(1):37-52.
- Friedländer MR, Chen W, Adamidi C, Maaskola J, Einspanier R, Knespel S, Rajewsky N. Discovering microRNAs from deep sequencing data using miRDeep.. Nat Biotechnol 2008 Apr;26(4):407-15.
- Langmead B, Trapnell C, Pop M, Salzberg SL. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.. Genome Biol 2009;10(3):R25.
- Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ. miRBase: microRNA sequences, targets and gene nomenclature.. Nucleic Acids Res 2006 Jan 1;34(Database issue):D140-4.
- Quinlan AR, Hall IM. BEDTools: a flexible suite of utilities for comparing genomic features.. Bioinformatics 2010 Mar 15;26(6):841-2.
- Koh W, Sheng CT, Tan B, Lee QY, Kuznetsov V, Kiang LS, Tanavde V. Analysis of deep sequencing microRNA expression profile from human embryonic stem cells derived mesenchymal stem cells reveals possible role of let-7 microRNA family in downstream targeting of hepatic nuclear factor 4 alpha.. BMC Genomics 2010 Feb 10;11 Suppl 1(Suppl 1):S6.
- Kraft M.F. GitHub. [(accessed on 15 September 2017)]; Available online: https://github.com/MatthiasKraft/Serum_miRNA_GENES.
- Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2.. Genome Biol 2014;15(12):550.
- Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data.. Bioinformatics 2010 Jan 1;26(1):139-40.
- Anders S, McCarthy DJ, Chen Y, Okoniewski M, Smyth GK, Huber W, Robinson MD. Count-based differential expression analysis of RNA sequencing data using R and Bioconductor.. Nat Protoc 2013 Sep;8(9):1765-86.
- Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets.. Cell 2005 Jan 14;120(1):15-20.
- Kinsella RJ, Kähäri A, Haider S, Zamora J, Proctor G, Spudich G, Almeida-King J, Staines D, Derwent P, Kerhornou A, Kersey P, Flicek P. Ensembl BioMarts: a hub for data retrieval across taxonomic space.. Database (Oxford) 2011;2011:bar030.
- Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium.. Nat Genet 2000 May;25(1):25-9.
- Nogales-Cadenas R, Carmona-Saez P, Vazquez M, Vicente C, Yang X, Tirado F, Carazo JM, Pascual-Montano A. GeneCodis: interpreting gene lists through enrichment analysis and integration of diverse biological information.. Nucleic Acids Res 2009 Jul;37(Web Server issue):W317-22.
- Tabas-Madrid D, Nogales-Cadenas R, Pascual-Montano A. GeneCodis3: a non-redundant and modular enrichment analysis tool for functional genomics.. Nucleic Acids Res 2012 Jul;40(Web Server issue):W478-83.
- Carmona-Saez P, Chagoyen M, Tirado F, Carazo JM, Pascual-Montano A. GENECODIS: a web-based tool for finding significant concurrent annotations in gene lists.. Genome Biol 2007;8(1):R3.
- Vlachos IS, Paraskevopoulou MD, Karagkouni D, Georgakilas G, Vergoulis T, Kanellos I, Anastasopoulos IL, Maniou S, Karathanou K, Kalfakakou D, Fevgas A, Dalamagas T, Hatzigeorgiou AG. DIANA-TarBase v7.0: indexing more than half a million experimentally supported miRNA:mRNA interactions.. Nucleic Acids Res 2015 Jan;43(Database issue):D153-9.
- Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform.. Bioinformatics 2009 Jul 15;25(14):1754-60.
- Langmead B, Salzberg SL. Fast gapped-read alignment with Bowtie 2.. Nat Methods 2012 Mar 4;9(4):357-9.
- Nawrocki EP, Burge SW, Bateman A, Daub J, Eberhardt RY, Eddy SR, Floden EW, Gardner PP, Jones TA, Tate J, Finn RD. Rfam 12.0: updates to the RNA families database.. Nucleic Acids Res 2015 Jan;43(Database issue):D130-7.
- Mueller RS, Janda J, Jensen-Jarolim E, Rhyner C, Marti E. Allergens in veterinary medicine.. Allergy 2016 Jan;71(1):27-35.
- Lee S, Hwang S, Yu HJ, Oh D, Choi YJ, Kim MC, Kim Y, Ryu DY. Expression of microRNAs in Horse Plasma and Their Characteristic Nucleotide Composition.. PLoS One 2016;11(1):e0146374.
- Pritchard CC, Kroh E, Wood B, Arroyo JD, Dougherty KJ, Miyaji MM, Tait JF, Tewari M. Blood cell origin of circulating microRNAs: a cautionary note for cancer biomarker studies.. Cancer Prev Res (Phila) 2012 Mar;5(3):492-497.
- Wang LS, Li L, Li L, Chu S, Shiang KD, Li M, Sun HY, Xu J, Xiao FJ, Sun G, Rossi JJ, Ho Y, Bhatia R. MicroRNA-486 regulates normal erythropoiesis and enhances growth and modulates drug response in CML progenitors.. Blood 2015 Feb 19;125(8):1302-13.
- Shaham L, Vendramini E, Ge Y, Goren Y, Birger Y, Tijssen MR, McNulty M, Geron I, Schwartzman O, Goldberg L, Chou ST, Pitman H, Weiss MJ, Michaeli S, Sredni B, Göttgens B, Crispino JD, Taub JW, Izraeli S. MicroRNA-486-5p is an erythroid oncomiR of the myeloid leukemias of Down syndrome.. Blood 2015 Feb 19;125(8):1292-301.
- Rüegger S, Großhans H. MicroRNA turnover: when, how, and why.. Trends Biochem Sci 2012 Oct;37(10):436-46.
- Hauser B, Zhao Y, Pang X, Ling Z, Myers E, Wang P, Califano J, Gu X. Functions of MiRNA-128 on the regulation of head and neck squamous cell carcinoma growth and apoptosis.. PLoS One 2015;10(3):e0116321.
- Hu J, Cheng Y, Li Y, Jin Z, Pan Y, Liu G, Fu S, Zhang Y, Feng K, Feng Y. microRNA-128 plays a critical role in human non-small cell lung cancer tumourigenesis, angiogenesis and lymphangiogenesis by directly targeting vascular endothelial growth factor-C.. Eur J Cancer 2014 Sep;50(13):2336-50.
- Sun J, Liao K, Wu X, Huang J, Zhang S, Lu X. Serum microRNA-128 as a biomarker for diagnosis of glioma.. Int J Clin Exp Med 2015;8(1):456-63.
- Adlakha YK, Saini N. miR-128 exerts pro-apoptotic effect in a p53 transcription-dependent and -independent manner via PUMA-Bak axis.. Cell Death Dis 2013 Mar 14;4(3):e542.
- Adlakha YK, Khanna S, Singh R, Singh VP, Agrawal A, Saini N. Pro-apoptotic miRNA-128-2 modulates ABCA1, ABCG1 and RXRα expression and cholesterol homeostasis.. Cell Death Dis 2013 Aug 29;4(8):e780.
- Bartner LR, Robinson NE, Kiupel M, Tesfaigzi Y. Persistent mucus accumulation: a consequence of delayed bronchial mucous cell apoptosis in RAO-affected horses?. Am J Physiol Lung Cell Mol Physiol 2006 Oct;291(4):L602-9.
- Moran G, Buechner-Maxwell VA, Folch H, Henriquez C, Galecio JS, Perez B, Carrasco C, Barria M. Increased apoptosis of CD4 and CD8 T lymphocytes in the airways of horses with recurrent airway obstruction.. Vet Res Commun 2011 Oct;35(7):447-56.
- Niedzwiedz A, Jaworski Z, Tykalowski B, Smialek M. Neutrophil and macrophage apoptosis in bronchoalveolar lavage fluid from healthy horses and horses with recurrent airway obstruction (RAO).. BMC Vet Res 2014 Jan 24;10:29.
- Martinez-Nunez RT, Bondanese VP, Louafi F, Francisco-Garcia AS, Rupani H, Bedke N, Holgate S, Howarth PH, Davies DE, Sanchez-Elsner T. A microRNA network dysregulated in asthma controls IL-6 production in bronchial epithelial cells.. PLoS One 2014;9(10):e111659.
- Rincon M, Irvin CG. Role of IL-6 in asthma and other inflammatory pulmonary diseases.. Int J Biol Sci 2012;8(9):1281-90.
- Ordoñez CL, Shaughnessy TE, Matthay MA, Fahy JV. Increased neutrophil numbers and IL-8 levels in airway secretions in acute severe asthma: Clinical and biologic significance.. Am J Respir Crit Care Med 2000 Apr;161(4 Pt 1):1185-90.
- Ainsworth DM, Grünig G, Matychak MB, Young J, Wagner B, Erb HN, Antczak DF. Recurrent airway obstruction (RAO) in horses is characterized by IFN-gamma and IL-8 production in bronchoalveolar lavage cells.. Vet Immunol Immunopathol 2003 Nov 15;96(1-2):83-91.
- Berndt A, Derksen FJ, Venta PJ, Karmaus W, Ewart S, Yuzbasiyan-Gurkan V, Robinson NE. Expression of toll-like receptor 2 mRNA in bronchial epithelial cells is not induced in RAO-affected horses.. Equine Vet J 2009 Jan;41(1):76-81.
- Ainsworth DM, Wagner B, Franchini M, Grünig G, Erb HN, Tan JY. Time-dependent alterations in gene expression of interleukin-8 in the bronchial epithelium of horses with recurrent airway obstruction.. Am J Vet Res 2006 Apr;67(4):669-77.
- Chu DK, Al-Garawi A, Llop-Guevara A, Pillai RA, Radford K, Shen P, Walker TD, Goncharova S, Calhoun WJ, Nair P, Jordana M. Therapeutic potential of anti-IL-6 therapies for granulocytic airway inflammation in asthma.. Allergy Asthma Clin Immunol 2015;11(1):14.
- Smolen JS, Maini RN. Interleukin-6: a new therapeutic target.. Arthritis Res Ther 2006;8 Suppl 2(Suppl 2):S5.
- Martin J, Jenkins RH, Bennagi R, Krupa A, Phillips AO, Bowen T, Fraser DJ. Post-transcriptional regulation of Transforming Growth Factor Beta-1 by microRNA-744.. PLoS One 2011;6(10):e25044.
- Debrue M, Hamilton E, Joubert P, Lajoie-Kadoch S, Lavoie JP. Chronic exacerbation of equine heaves is associated with an increased expression of interleukin-17 mRNA in bronchoalveolar lavage cells.. Vet Immunol Immunopathol 2005 May 1;105(1-2):25-31.
- Newcomb DC, Peebles RS Jr. Th17-mediated inflammation in asthma.. Curr Opin Immunol 2013 Dec;25(6):755-60.
- Wang H, Su X, Yang M, Chen T, Hou J, Li N, Cao X. Reciprocal control of miR-197 and IL-6/STAT3 pathway reveals miR-197 as potential therapeutic target for hepatocellular carcinoma.. Oncoimmunology 2015 Oct;4(10):e1031440.
- Yang XO, Panopoulos AD, Nurieva R, Chang SH, Wang D, Watowich SS, Dong C. STAT3 regulates cytokine-mediated generation of inflammatory helper T cells.. J Biol Chem 2007 Mar 30;282(13):9358-9363.
- Chalmin F, Mignot G, Bruchard M, Chevriaux A, Végran F, Hichami A, Ladoire S, Derangère V, Vincent J, Masson D, Robson SC, Eberl G, Pallandre JR, Borg C, Ryffel B, Apetoh L, Rébé C, Ghiringhelli F. Stat3 and Gfi-1 transcription factors control Th17 cell immunosuppressive activity via the regulation of ectonucleotidase expression.. Immunity 2012 Mar 23;36(3):362-73.
- Takagi R, Higashi T, Hashimoto K, Nakano K, Mizuno Y, Okazaki Y, Matsushita S. B cell chemoattractant CXCL13 is preferentially expressed by human Th17 cell clones.. J Immunol 2008 Jul 1;181(1):186-9.
- Eddens T, Elsegeiny W, Garcia-Hernadez ML, Castillo P, Trevejo-Nunez G, Serody K, Campfield BT, Khader SA, Chen K, Rangel-Moreno J, Kolls JK. Pneumocystis-Driven Inducible Bronchus-Associated Lymphoid Tissue Formation Requires Th2 and Th17 Immunity.. Cell Rep 2017 Mar 28;18(13):3078-3090.
- Elliot JG, Jensen CM, Mutavdzic S, Lamb JP, Carroll NG, James AL. Aggregations of lymphoid cells in the airways of nonsmokers, smokers, and subjects with asthma.. Am J Respir Crit Care Med 2004 Mar 15;169(6):712-8.
- Damsker JM, Hansen AM, Caspi RR. Th1 and Th17 cells: adversaries and collaborators.. Ann N Y Acad Sci 2010 Jan;1183:211-21.
- Irvin C, Zafar I, Good J, Rollins D, Christianson C, Gorska MM, Martin RJ, Alam R. Increased frequency of dual-positive TH2/TH17 cells in bronchoalveolar lavage fluid characterizes a population of patients with severe asthma.. J Allergy Clin Immunol 2014 Nov;134(5):1175-1186.e7.
- Takahashi Y, Forrest AR, Maeno E, Hashimoto T, Daub CO, Yasuda J. MiR-107 and MiR-185 can induce cell cycle arrest in human non small cell lung cancer cell lines.. PLoS One 2009 Aug 18;4(8):e6677.
- Xia W, Ni J, Zhuang J, Qian L, Wang P, Wang J. MiR-103 regulates hepatocellular carcinoma growth by targeting AKAP12.. Int J Biochem Cell Biol 2016 Feb;71:1-11.
- Badalà F, Nouri-mahdavi K, Raoof DA. Expansion of an atypical NK cell subset in mouse models of SLE. Computer (Long. Beach. Calif) 2008;144:724–732.
- Ballabio E, Mitchell T, van Kester MS, Taylor S, Dunlop HM, Chi J, Tosi I, Vermeer MH, Tramonti D, Saunders NJ, Boultwood J, Wainscoat JS, Pezzella F, Whittaker SJ, Tensen CP, Hatton CS, Lawrie CH. MicroRNA expression in Sezary syndrome: identification, function, and diagnostic potential.. Blood 2010 Aug 19;116(7):1105-13.
- Akbas F, Coskunpinar E, Aynaci E, Oltulu YM, Yildiz P. Analysis of serum micro-RNAs as potential biomarker in chronic obstructive pulmonary disease.. Exp Lung Res 2012 Aug;38(6):286-94.
- Hong CF, Lin SY, Chou YT, Wu CW. MicroRNA-7 Compromises p53 Protein-dependent Apoptosis by Controlling the Expression of the Chromatin Remodeling Factor SMARCD1.. J Biol Chem 2016 Jan 22;291(4):1877-1889.
- Porto IO, Mendes-Junior CT, Felício LP, Georg RC, Moreau P, Donadi EA, Chies JA, Castelli EC. MicroRNAs targeting the immunomodulatory HLA-G gene: a new survey searching for microRNAs with potential to regulate HLA-G.. Mol Immunol 2015 Jun;65(2):230-41.
- Tan Z, Randall G, Fan J, Camoretti-Mercado B, Brockman-Schneider R, Pan L, Solway J, Gern JE, Lemanske RF, Nicolae D. Allele-Specific Targeting of microRNAs to HLA-G and Risk of Asthma (PII:S0002-9297(07)63059-6). Am. J. Hum. Genet. 2008;82:251.
- Enomoto Y, Takagi R, Naito Y, Kiniwa T, Tanaka Y, Hamada-Tsutsumi S, Kawano M, Matsushita S, Ochiya T, Miyajima A. Identification of the novel 3' UTR sequences of human IL-21 mRNA as potential targets of miRNAs.. Sci Rep 2017 Aug 10;7(1):7780.
- Sun Y, Pan J, Mao S, Jin J. IL-17/miR-192/IL-17Rs regulatory feedback loop facilitates multiple myeloma progression.. PLoS One 2014;9(12):e114647.
- McGeachie MJ, Davis JS, Kho AT, Dahlin A, Sordillo JE, Sun M, Lu Q, Weiss ST, Tantisira KG. Asthma remission: Predicting future airways responsiveness using an miRNA network.. J Allergy Clin Immunol 2017 Aug;140(2):598-600.e8.
- Pereira-Leal JB, Seabra MC. Evolution of the Rab family of small GTP-binding proteins.. J Mol Biol 2001 Nov 2;313(4):889-901.
- Seto S, Tsujimura K, Koide Y. Rab GTPases regulating phagosome maturation are differentially recruited to mycobacterial phagosomes.. Traffic 2011 Apr;12(4):407-20.
- Ding L, Abebe T, Beyene J, Wilke RA, Goldberg A, Woo JG, Martin LJ, Rothenberg ME, Rao M, Hershey GK, Chakraborty R, Mersha TB. Rank-based genome-wide analysis reveals the association of ryanodine receptor-2 gene variants with childhood asthma among human populations.. Hum Genomics 2013 Jul 5;7(1):16.
- Probert K, Miller S, Kheirallah AK, Hall IP. Developmental genetics of the COPD lung. COPD Res. Pract. 2015;1:10.
- Tang W, Kowgier M, Loth DW, Soler Artigas M, Joubert BR, Hodge E, Gharib SA, Smith AV, Ruczinski I, Gudnason V, Mathias RA, Harris TB, Hansel NN, Launer LJ, Barnes KC, Hansen JG, Albrecht E, Aldrich MC, Allerhand M, Barr RG, Brusselle GG, Couper DJ, Curjuric I, Davies G, Deary IJ, Dupuis J, Fall T, Foy M, Franceschini N, Gao W, Gläser S, Gu X, Hancock DB, Heinrich J, Hofman A, Imboden M, Ingelsson E, James A, Karrasch S, Koch B, Kritchevsky SB, Kumar A, Lahousse L, Li G, Lind L, Lindgren C, Liu Y, Lohman K, Lumley T, McArdle WL, Meibohm B, Morris AP, Morrison AC, Musk B, North KE, Palmer LJ, Probst-Hensch NM, Psaty BM, Rivadeneira F, Rotter JI, Schulz H, Smith LJ, Sood A, Starr JM, Strachan DP, Teumer A, Uitterlinden AG, Völzke H, Voorman A, Wain LV, Wells MT, Wilk JB, Williams OD, Heckbert SR, Stricker BH, London SJ, Fornage M, Tobin MD, O'Connor GT, Hall IP, Cassano PA. Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.. PLoS One 2014;9(7):e100776.
- Szabo SJ, Kim ST, Costa GL, Zhang X, Fathman CG, Glimcher LH. A novel transcription factor, T-bet, directs Th1 lineage commitment.. Cell 2000 Mar 17;100(6):655-69.
- Mullen AC, Hutchins AS, High FA, Lee HW, Sykes KJ, Chodosh LA, Reiner SL. Hlx is induced by and genetically interacts with T-bet to promote heritable T(H)1 gene induction.. Nat Immunol 2002 Jul;3(7):652-8.
- Casaca VI, Illi S, Suttner K, Schleich I, Ballenberger N, Klucker E, Turan E, von Mutius E, Kabesch M, Schaub B. TBX21 and HLX1 polymorphisms influence cytokine secretion at birth.. PLoS One 2012;7(1):e31069.
- Murphy TM, Wong CC, Arseneault L, Burrage J, Macdonald R, Hannon E, Fisher HL, Ambler A, Moffitt TE, Caspi A, Mill J. Methylomic markers of persistent childhood asthma: a longitudinal study of asthma-discordant monozygotic twins.. Clin Epigenetics 2015;7:130.
- Suttner K, Rosenstiel P, Depner M, Schedel M, Pinto LA, Ruether A, Adamski J, Klopp N, Illig T, Vogelberg C, Schreiber S, von Mutius E, Kabesch M. TBX21 gene variants increase childhood asthma risk in combination with HLX1 variants.. J Allergy Clin Immunol 2009 May;123(5):1062-8, 1068.e1-8.
- Suttner K, Ruoss I, Rosenstiel P, Depner M, Pinto LA, Schedel M, Adamski J, Illig T, Schreiber S, von Mutius E, Kabesch M. HLX1 gene variants influence the development of childhood asthma.. J Allergy Clin Immunol 2009 Jan;123(1):82-88.e6.
- Wenzel SE. Asthma phenotypes: the evolution from clinical to molecular approaches.. Nat Med 2012 May 4;18(5):716-25.
- Raundhal M, Morse C, Khare A, Oriss TB, Milosevic J, Trudeau J, Huff R, Pilewski J, Holguin F, Kolls J, Wenzel S, Ray P, Ray A. High IFN-γ and low SLPI mark severe asthma in mice and humans.. J Clin Invest 2015 Aug 3;125(8):3037-50.
- Hackett TL. Epithelial-mesenchymal transition in the pathophysiology of airway remodelling in asthma.. Curr Opin Allergy Clin Immunol 2012 Feb;12(1):53-9.
- Ijaz T, Pazdrak K, Kalita M, Konig R, Choudhary S, Tian B, Boldogh I, Brasier AR. Systems biology approaches to understanding Epithelial Mesenchymal Transition (EMT) in mucosal remodeling and signaling in asthma.. World Allergy Organ J 2014;7(1):13.
- Han JM, Patterson SJ, Levings MK. The Role of the PI3K Signaling Pathway in CD4(+) T Cell Differentiation and Function.. Front Immunol 2012;3:245.
- Wang J, Li F, Yang M, Wu J, Zhao J, Gong W, Liu W, Bi W, Dong L. FIZZ1 promotes airway remodeling through the PI3K/Akt signaling pathway in asthma.. Exp Ther Med 2014 May;7(5):1265-1270.
- Sheller JR, Polosukhin VV, Mitchell D, Cheng DS, Peebles RS, Blackwell TS. Nuclear factor kappa B induction in airway epithelium increases lung inflammation in allergen-challenged mice.. Exp Lung Res 2009 Dec;35(10):883-95.
- Graham JA, Fray M, de Haseth S, Lee KM, Lian MM, Chase CM, Madsen JC, Markmann J, Benichou G, Colvin RB, Cosimi AB, Deng S, Kim J, Alessandrini A. Suppressive regulatory T cell activity is potentiated by glycogen synthase kinase 3{beta} inhibition.. J Biol Chem 2010 Oct 22;285(43):32852-32859.
- Fu R, Li J, Zhong H, Yu D, Zeng X, Deng M, Sun Y, Wen W, Li H. Broncho-Vaxom attenuates allergic airway inflammation by restoring GSK3β-related T regulatory cell insufficiency.. PLoS One 2014;9(3):e92912.
- Coutaz M, Hurrell BP, Auderset F, Wang H, Siegert S, Eberl G, Ho PC, Radtke F, Tacchini-Cottier F. Notch regulates Th17 differentiation and controls trafficking of IL-17 and metabolic regulators within Th17 cells in a context-dependent manner.. Sci Rep 2016 Dec 15;6:39117.
- Hernandez JB, Chang C, LeBlanc M, Grimm D, Le Lay J, Kaestner KH, Zheng Y, Montminy M. The CREB/CRTC2 pathway modulates autoimmune disease by promoting Th17 differentiation.. Nat Commun 2015 Jun 2;6:7216.
- Lane SJ, Adcock IM, Richards D, Hawrylowicz C, Barnes PJ, Lee TH. Corticosteroid-resistant bronchial asthma is associated with increased c-fos expression in monocytes and T lymphocytes.. J Clin Invest 1998 Dec 15;102(12):2156-64.
- Janssen-Heininger YM, Poynter ME, Aesif SW, Pantano C, Ather JL, Reynaert NL, Ckless K, Anathy V, van der Velden J, Irvin CG, van der Vliet A. Nuclear factor kappaB, airway epithelium, and asthma: avenues for redox control.. Proc Am Thorac Soc 2009 May 1;6(3):249-55.
- Ren Y, Su X, Kong L, Li M, Zhao X, Yu N, Kang J. Therapeutic effects of histone deacetylase inhibitors in a murine asthma model.. Inflamm Res 2016 Dec;65(12):995-1008.
- DuPage M, Bluestone JA. Harnessing the plasticity of CD4(+) T cells to treat immune-mediated disease.. Nat Rev Immunol 2016 Mar;16(3):149-63.
- Leclere M, Lavoie-Lamoureux A, Lavoie JP. Heaves, an asthma-like disease of horses.. Respirology 2011 Oct;16(7):1027-46.
- Lee CT, Risom T, Strauss WM. Evolutionary conservation of microRNA regulatory circuits: an examination of microRNA gene complexity and conserved microRNA-target interactions through metazoan phylogeny.. DNA Cell Biol 2007 Apr;26(4):209-18.
Citations
This article has been cited 19 times.- Riihimäki M, Fegraeus K, Nordlund J, Waern I, Wernersson S, Akula S, Hellman L, Raine A. Single-cell transcriptomics delineates the immune cell landscape in equine lower airways and reveals upregulation of FKBP5 in horses with asthma.. Sci Rep 2023 Sep 27;13(1):16261.
- Sweef O, Zaabout E, Bakheet A, Halawa M, Gad I, Akela M, Tousson E, Abdelghany A, Furuta S. Unraveling Therapeutic Opportunities and the Diagnostic Potential of microRNAs for Human Lung Cancer.. Pharmaceutics 2023 Jul 31;15(8).
- Elkommos-Zakhary M, Rajesh N, Beljanski V. Exosome RNA Sequencing as a Tool in the Search for Cancer Biomarkers.. Noncoding RNA 2022 Nov 9;8(6).
- Janssen P, Tosi I, Hego A, Maréchal P, Marichal T, Radermecker C. Neutrophil Extracellular Traps Are Found in Bronchoalveolar Lavage Fluids of Horses With Severe Asthma and Correlate With Asthma Severity.. Front Immunol 2022;13:921077.
- Simões J, Batista M, Tilley P. The Immune Mechanisms of Severe Equine Asthma-Current Understanding and What Is Missing.. Animals (Basel) 2022 Mar 16;12(6).
- Song D, Jiang Y, Zhao Q, Li J, Zhao Y. lncRNA-NEAT1 Sponges miR-128 to Promote Inflammatory Reaction and Phenotypic Transformation of Airway Smooth Muscle Cells.. Comput Math Methods Med 2022;2022:7499911.
- Wang X, Chen H, Liu J, Gai L, Yan X, Guo Z, Liu F. Emerging Advances of Non-coding RNAs and Competitive Endogenous RNA Regulatory Networks in Asthma.. Bioengineered 2021 Dec;12(1):7820-7836.
- Srinivasan A, Sundar IK. Recent updates on the role of extracellular vesicles in the pathogenesis of allergic asthma.. Extracell Vesicles Circ Nucl Acids 2021;2:127-147.
- Anderson ED, Alishahedani ME, Myles IA. Epithelial-Mesenchymal Transition in Atopy: A Mini-Review.. Front Allergy 2020 Dec;1.
- Alashkar Alhamwe B, Potaczek DP, Miethe S, Alhamdan F, Hintz L, Magomedov A, Garn H. Extracellular Vesicles and Asthma-More Than Just a Co-Existence.. Int J Mol Sci 2021 May 7;22(9).
- Wang J, Zhang Y, Li H, Chen G, Zou Y, Rin K. Immune effects of miRNA and Th17 cells on β-Lg allergy in dietary milk based on mouse model.. Saudi J Biol Sci 2020 Dec;27(12):3442-3448.
- Hulliger MF, Pacholewska A, Vargas A, Lavoie JP, Leeb T, Gerber V, Jagannathan V. An Integrative miRNA-mRNA Expression Analysis Reveals Striking Transcriptomic Similarities between Severe Equine Asthma and Specific Asthma Endotypes in Humans.. Genes (Basel) 2020 Sep 28;11(10).
- Couetil L, Cardwell JM, Leguillette R, Mazan M, Richard E, Bienzle D, Bullone M, Gerber V, Ivester K, Lavoie JP, Martin J, Moran G, Niedźwiedź A, Pusterla N, Swiderski C. Equine Asthma: Current Understanding and Future Directions.. Front Vet Sci 2020;7:450.
- Sheats MK, Davis KU, Poole JA. Comparative Review of Asthma in Farmers and Horses.. Curr Allergy Asthma Rep 2019 Oct 10;19(11):50.
- Huang F, Bai J, Zhang J, Yang D, Fan H, Huang L, Shi T, Lu G. Identification of potential diagnostic biomarkers for pneumonia caused by adenovirus infection in children by screening serum exosomal microRNAs.. Mol Med Rep 2019 May;19(5):4306-4314.
- Huang H, Lu H, Liang L, Zhi Y, Huo B, Wu L, Xu L, Shen Z. MicroRNA-744 Inhibits Proliferation of Bronchial Epithelial Cells by Regulating Smad3 Pathway via Targeting Transforming Growth Factor-β1 (TGF-β1) in Severe Asthma.. Med Sci Monit 2019 Mar 23;25:2159-2168.
- Bond S, Léguillette R, Richard EA, Couetil L, Lavoie JP, Martin JG, Pirie RS. Equine asthma: Integrative biologic relevance of a recently proposed nomenclature.. J Vet Intern Med 2018 Nov;32(6):2088-2098.
- Galeone C, Scelfo C, Bertolini F, Caminati M, Ruggiero P, Facciolongo N, Menzella F. Precision Medicine in Targeted Therapies for Severe Asthma: Is There Any Place for "Omics" Technology?. Biomed Res Int 2018;2018:4617565.
- Carossino M, Dini P, Kalbfleisch TS, Loynachan AT, Canisso IF, Shuck KM, Timoney PJ, Cook RF, Balasuriya UBR. Downregulation of MicroRNA eca-mir-128 in Seminal Exosomes and Enhanced Expression of CXCL16 in the Stallion Reproductive Tract Are Associated with Long-Term Persistence of Equine Arteritis Virus.. J Virol 2018 May 1;92(9).
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists