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Home / Equine Research Bank / PLoS One / Profiling of differentially expressed genes using suppressio...
PloS one2012; 7(1); e29440; doi: 10.1371/journal.pone.0029440

Profiling of differentially expressed genes using suppression subtractive hybridization in an equine model of chronic asthma.

Abstract: Gene expression analyses are used to investigate signaling pathways involved in diseases. In asthma, they have been primarily derived from the analysis of bronchial biopsies harvested from mild to moderate asthmatic subjects and controls. Due to ethical considerations, there is currently limited information on the transcriptome profile of the peripheral lung tissues in asthma. Objective: To identify genes contributing to chronic inflammation and remodeling in the peripheral lung tissue of horses with heaves, a naturally occurring asthma-like condition. Methods: Eleven adult horses (6 heaves-affected and 5 controls) were studied while horses with heaves were in clinical remission (Pasture), and during disease exacerbation induced by a 30-day natural antigen challenge during stabling (Challenge). Large peripheral lung biopsies were obtained by thoracoscopy at both time points. Using suppression subtractive hybridization (SSH), lung cDNAs of controls (Pasture and Challenge) and asymptomatic heaves-affected horses (Pasture) were subtracted from cDNAs of horses with heaves in clinical exacerbation (Challenge). The differential expression of selected genes of interest was confirmed using quantitative PCR assay. Results: Horses with heaves, but not controls, developed airway obstruction when challenged. Nine hundred and fifty cDNA clones isolated from the subtracted library were screened by dot blot array and 224 of those showing the most marked expression differences were sequenced. The gene expression pattern was confirmed by quantitative PCR in 15 of 22 selected genes. Novel genes and genes with an already defined function in asthma were identified in the subtracted cDNA library. Genes of particular interest associated with asthmatic airway inflammation and remodeling included those related to PPP3CB/NFAT, RhoA, and LTB4/GPR44 signaling pathways. Conclusions: Pathways representing new possible targets for anti-inflammatory and anti-remodeling therapies for asthma were identified. The findings of genes previously associated with asthma validate this equine model for gene expression studies.
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Publication Date: 2012-01-03 PubMed ID: 22235296PubMed Central: PMC3250435DOI: 10.1371/journal.pone.0029440Google Scholar: Lookup
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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.

The research article presents a study on how gene expression analyses are used to investigate signalling pathways involved in asthma, using an equine model, with a specific focus on chronic inflammation and remodeling in the peripheral lung tissue of horses with heaves, an asthma-like condition.

Objectives and Methodology of the Study

  • The aim of the study was to identify genes contributing to chronic inflammation and remodeling in the peripheral lung tissue of horses with a condition known as heaves, an analogous condition to human asthma.
  • The researchers studied 11 adult horses, 6 of which were affected by heaves and 5 were controls. The horses were studied during clinical remission and during disease exacerbation induced by a 30-day natural antigen challenge.
  • Large peripheral lung biopsies were obtained from the horses at both time points using a procedure known as thoracoscopy.
  • A technique known as suppression subtractive hybridization (SSH) was used to compare gene expression between the control horses and the ones affected by heaves. This technique allows researchers to compare two RNA samples and identify the differences between them.
  • The differential expression of selected genes was then confirmed using a quantitative PCR assay, a common method for measuring the amount of a specific RNA.

    • Results of the Study

    • The study found that horses with heaves, but not the controls, developed airway obstruction when challenged.
    • 950 clones isolated from the subtracted library were analyzed and 224 of those showing the most significant expression differences were sequenced for further investigation.
    • The study confirmed the differential expression of 15 out of 22 selected genes using a quantitative PCR.
    • The identified genes included both novel genes and genes already associated with asthma, reinforcing the validity of the available equine model for gene expression studies in this area.
    • Particular genes associated with asthmatic airway inflammation and remodeling, relating to PPP3CB/NFAT, RhoA, and LTB4/GPR44 signaling pathways were identified.

    Conclusions and Implications

    • The study points out potential new targets for anti-inflammatory and anti-remodeling therapies for asthma, enhancing our understanding of the genetic basis of asthmatic conditions and potentially contributing to the development of new treatment strategies.
    • The identified genes could become the focus of future research and aid in gaining a better understanding of the molecular mechanisms and signaling pathways involved in asthma and similar chronic respiratory diseases.
    • The successful use of the equine model validates its application for similar gene expression studies, potentially paving the way for more extensive application in future research.

Cite This Article

APA
Lavoie JP, Lefebvre-Lavoie J, Leclere M, Lavoie-Lamoureux A, Chamberland A, Laprise C, Lussier J. (2012). Profiling of differentially expressed genes using suppression subtractive hybridization in an equine model of chronic asthma. PLoS One, 7(1), e29440. https://doi.org/10.1371/journal.pone.0029440

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 7
Issue: 1
Pages: e29440
PII: e29440

Researcher Affiliations

Lavoie, Jean-Pierre
  • Department of Clinical Sciences, Faculty of Veterinary Medicine, Université de Montréal, Saint-Hyacinthe, Q, Canada. jean-pierre.lavoie@umontreal.ca
Lefebvre-Lavoie, Josiane
    Leclere, Mathilde
      Lavoie-Lamoureux, Anouk
        Chamberland, Annie
          Laprise, Catherine
            Lussier, Jacques

              MeSH Terms

              • Animals
              • Antigens / immunology
              • Asthma / genetics
              • Chronic Disease
              • Cloning, Molecular
              • Disease Models, Animal
              • Female
              • Gene Expression Profiling / methods
              • Gene Library
              • Horses
              • Lung / immunology
              • Lung / metabolism
              • Male
              • Polymerase Chain Reaction

              Grant Funding

              • MIF79636 / Canadian Institutes of Health Research

              Conflict of Interest Statement

              The authors have declared that no competing interests exist.

              References

              This article includes 70 references
              1. Elias JA. Airway remodeling in asthma. Unanswered questions.. Am J Respir Crit Care Med 2000 Mar;161(3 Pt 2):S168-71.
                pubmed: 10712368doi: 10.1164/ajrccm.161.supplement_2.a1q4-4google scholar: lookup
              2. James A. Airway remodeling in asthma.. Curr Opin Pulm Med 2005 Jan;11(1):1-6.
                pubmed: 15591881doi: 10.1097/01.mcp.0000146779.26339.d8google scholar: lookup
              3. Hansel NN, Diette GB. Gene expression profiling in human asthma.. Proc Am Thorac Soc 2007 Jan;4(1):32-6.
                pmc: PMC2647611pubmed: 17202289doi: 10.1513/pats.200606-132JGgoogle scholar: lookup
              4. Homer RJ, Elias JA. Airway remodeling in asthma: therapeutic implications of mechanisms.. Physiology (Bethesda) 2005 Feb;20:28-35.
                pubmed: 15653837doi: 10.1152/physiol.00035.2004google scholar: lookup
              5. Jeffery PK. Investigation and assessment of airway and lung inflammation: we now have the tools, what are the questions?. Eur Respir J 1998 Mar;11(3):524-8.
                pubmed: 9596096
              6. Karol MH. Animal models of occupational asthma.. Eur Respir J 1994 Mar;7(3):555-68.
                pubmed: 8013613doi: 10.1183/09031936.94.07030555google scholar: lookup
              7. McLaughlin RF Jr. Bronchial artery distribution in various mammals and in humans.. Am Rev Respir Dis 1983 Aug;128(2 Pt 2):S57-8.
                pubmed: 6881710doi: 10.1164/arrd.1983.128.2P2.S57google scholar: lookup
              8. Magno M. Comparative anatomy of the tracheobronchial circulation.. Eur Respir J Suppl 1990 Dec;12:557s-562s; discussion 562s-563s.
                pubmed: 2127528
              9. van Erck E, Votion DM, Kirschvink N, Art T, Lekeux P. Use of the impulse oscillometry system for testing pulmonary function during methacholine bronchoprovocation in horses.. Am J Vet Res 2003 Nov;64(11):1414-20.
                pubmed: 14620779doi: 10.2460/ajvr.2003.64.1414google scholar: lookup
              10. LOWELL FC. OBSERVATIONS ON HEAVES. AN ASTHMA-LIKE SYNDROME IN THE HORSE.. J Allergy 1964 Jul-Aug;35:322-30.
                pubmed: 14193184doi: 10.1016/0021-8707(64)90095-4google scholar: lookup
              11. Snapper JR. Large animal models of asthma.. Am Rev Respir Dis 1986 Mar;133(3):351-2.
                pubmed: 3082262doi: 10.1164/arrd.1986.133.3.351google scholar: lookup
              12. Robinson NE. International Workshop on Equine Chronic Airway Disease. Michigan State University 16-18 June 2000.. Equine Vet J 2001 Jan;33(1):5-19.
                pubmed: 11191611doi: 10.2746/042516401776767412google scholar: lookup
              13. Range F, Mundhenk L, Gruber AD. A soluble secreted glycoprotein (eCLCA1) is overexpressed due to goblet cell hyperplasia and metaplasia in horses with recurrent airway obstruction.. Vet Pathol 2007 Nov;44(6):901-11.
                pubmed: 18039903doi: 10.1354/vp.44-6-901google scholar: lookup
              14. 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.
                pubmed: 16890762doi: 10.1016/j.jaci.2006.03.044google scholar: lookup
              15. Leclere M, Lavoie-Lamoureux A, Gélinas-Lymburner E, David F, Martin JG, Lavoie JP. Effect of antigenic exposure on airway smooth muscle remodeling in an equine model of chronic asthma.. Am J Respir Cell Mol Biol 2011 Jul;45(1):181-7.
                pubmed: 20935189doi: 10.1165/rcmb.2010-0300OCgoogle scholar: lookup
              16. Cao W, Epstein C, Liu H, DeLoughery C, Ge N, Lin J, Diao R, Cao H, Long F, Zhang X, Chen Y, Wright PS, Busch S, Wenck M, Wong K, Saltzman AG, Tang Z, Liu L, Zilberstein A. Comparing gene discovery from Affymetrix GeneChip microarrays and Clontech PCR-select cDNA subtraction: a case study.. BMC Genomics 2004 Apr 27;5(1):26.
                pmc: PMC415544pubmed: 15113399doi: 10.1186/1471-2164-5-26google scholar: lookup
              17. Qin M, Zeng Z, Zheng J, Shah PK, Schwartz SM, Adams LD, Sharifi BG. Suppression subtractive hybridization identifies distinctive expression markers for coronary and internal mammary arteries.. Arterioscler Thromb Vasc Biol 2003 Mar 1;23(3):425-33.
                pmc: PMC3579564pubmed: 12615697doi: 10.1161/01.ATV.0000059303.94760.5Cgoogle scholar: lookup
              18. McClintock TS. High-throughput expression profiling techniques.. Chem Senses 2002 Mar;27(3):289-91.
                pubmed: 11923190doi: 10.1093/chemse/27.3.289google scholar: lookup
              19. Relave F, David F, Leclère M, Alexander K, Bussières G, Lavoie JP, Marcoux M. Evaluation of a thoracoscopic technique using ligating loops to obtain large lung biopsies in standing healthy and heaves-affected horses.. Vet Surg 2008 Apr;37(3):232-40.
                pubmed: 18394069doi: 10.1111/j.1532-950X.2008.00371.xgoogle scholar: lookup
              20. Bédard J, Brûlé S, Price CA, Silversides DW, Lussier JG. Serine protease inhibitor-E2 (SERPINE2) is differentially expressed in granulosa cells of dominant follicle in cattle.. Mol Reprod Dev 2003 Feb;64(2):152-65.
                pubmed: 12506347doi: 10.1002/mrd.10239google scholar: lookup
              21. Fayad T, Lévesque V, Sirois J, Silversides DW, Lussier JG. Gene expression profiling of differentially expressed genes in granulosa cells of bovine dominant follicles using suppression subtractive hybridization.. Biol Reprod 2004 Feb;70(2):523-33.
                pubmed: 14568916doi: 10.1095/biolreprod.103.021709google scholar: lookup
              22. Ekberg-Jansson A, Andersson B, Bake B, Boijsen M, Enanden I, Rosengren A, Skoogh BE, Tylén U, Venge P, Löfdahl CG. Neutrophil-associated activation markers in healthy smokers relates to a fall in DL(CO) and to emphysematous changes on high resolution CT.. Respir Med 2001 May;95(5):363-73.
                pubmed: 11392577doi: 10.1053/rmed.2001.1050google scholar: lookup
              23. Andersen CL, Jensen JL, Ørntoft TF. Normalization of real-time quantitative reverse transcription-PCR data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets.. Cancer Res 2004 Aug 1;64(15):5245-50.
                pubmed: 15289330doi: 10.1158/0008-5472.CAN-04-0496google scholar: lookup
              24. Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes.. Genome Biol 2002 Jun 18;3(7):RESEARCH0034.
                pmc: PMC126239pubmed: 12184808doi: 10.1186/gb-2002-3-7-research0034google scholar: lookup
              25. Pfaffl MW, Horgan GW, Dempfle L. Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR.. Nucleic Acids Res 2002 May 1;30(9):e36.
                pmc: PMC113859pubmed: 11972351doi: 10.1093/nar/30.9.e36google scholar: lookup
              26. Bustin SA. Quantification of mRNA using real-time reverse transcription PCR (RT-PCR): trends and problems.. J Mol Endocrinol 2002 Aug;29(1):23-39.
                pubmed: 12200227doi: 10.1677/jme.0.0290023google scholar: lookup
              27. Anderson GP. Endotyping asthma: new insights into key pathogenic mechanisms in a complex, heterogeneous disease.. Lancet 2008 Sep 20;372(9643):1107-19.
                pubmed: 18805339doi: 10.1016/S0140-6736(08)61452-Xgoogle scholar: lookup
              28. James AL, Paré PD, Hogg JC. The mechanics of airway narrowing in asthma.. Am Rev Respir Dis 1989 Jan;139(1):242-6.
                pubmed: 2912345doi: 10.1164/ajrccm/139.1.242google scholar: lookup
              29. Bai TR. Evidence for airway remodeling in chronic asthma.. Curr Opin Allergy Clin Immunol 2010 Feb;10(1):82-6.
                pubmed: 19858714doi: 10.1097/ACI.0b013e32833363b2google scholar: lookup
              30. Hirota JA, Nguyen TT, Schaafsma D, Sharma P, Tran T. Airway smooth muscle in asthma: phenotype plasticity and function.. Pulm Pharmacol Ther 2009 Oct;22(5):370-8.
                pubmed: 19114115doi: 10.1016/j.pupt.2008.12.004google scholar: lookup
              31. Mao J, Yuan H, Xie W, Wu D. Guanine nucleotide exchange factor GEF115 specifically mediates activation of Rho and serum response factor by the G protein alpha subunit Galpha13.. Proc Natl Acad Sci U S A 1998 Oct 27;95(22):12973-6.
                pmc: PMC23675pubmed: 9789025doi: 10.1073/pnas.95.22.12973google scholar: lookup
              32. Lee SM, Vasishtha M, Prywes R. Activation and repression of cellular immediate early genes by serum response factor cofactors.. J Biol Chem 2010 Jul 16;285(29):22036-49.
                pmc: PMC2903344pubmed: 20466732doi: 10.1074/jbc.M110.108878google scholar: lookup
              33. Wang Z, Wang DZ, Hockemeyer D, McAnally J, Nordheim A, Olson EN. Myocardin and ternary complex factors compete for SRF to control smooth muscle gene expression.. Nature 2004 Mar 11;428(6979):185-9.
                pubmed: 15014501doi: 10.1038/nature02382google scholar: lookup
              34. Yoshii A, Iizuka K, Dobashi K, Horie T, Harada T, Nakazawa T, Mori M. Relaxation of contracted rabbit tracheal and human bronchial smooth muscle by Y-27632 through inhibition of Ca2+ sensitization.. Am J Respir Cell Mol Biol 1999 Jun;20(6):1190-200.
                pubmed: 10340938doi: 10.1165/ajrcmb.20.6.3441google scholar: lookup
              35. Kay AB, Ying S, Varney V, Gaga M, Durham SR, Moqbel R, Wardlaw AJ, Hamid Q. Messenger RNA expression of the cytokine gene cluster, interleukin 3 (IL-3), IL-4, IL-5, and granulocyte/macrophage colony-stimulating factor, in allergen-induced late-phase cutaneous reactions in atopic subjects.. J Exp Med 1991 Mar 1;173(3):775-8.
                pmc: PMC2118805pubmed: 1997656doi: 10.1084/jem.173.3.775google scholar: lookup
              36. Schaafsma D, Gosens R, Zaagsma J, Halayko AJ, Meurs H. Rho kinase inhibitors: a novel therapeutical intervention in asthma?. Eur J Pharmacol 2008 May 13;585(2-3):398-406.
                pubmed: 18410919doi: 10.1016/j.ejphar.2008.01.056google scholar: lookup
              37. Yang SH, Yates PR, Whitmarsh AJ, Davis RJ, Sharrocks AD. The Elk-1 ETS-domain transcription factor contains a mitogen-activated protein kinase targeting motif.. Mol Cell Biol 1998 Feb;18(2):710-20.
                pmc: PMC108782pubmed: 9447967doi: 10.1128/MCB.18.2.710google scholar: lookup
              38. Ohkawa Y, Hayashi K, Sobue K. Calcineurin-mediated pathway involved in the differentiated phenotype of smooth muscle cells.. Biochem Biophys Res Commun 2003 Jan 31;301(1):78-83.
                pubmed: 12535643doi: 10.1016/s0006-291x(02)02965-0google scholar: lookup
              39. Kakita T, Hasegawa K, Iwai-Kanai E, Adachi S, Morimoto T, Wada H, Kawamura T, Yanazume T, Sasayama S. Calcineurin pathway is required for endothelin-1-mediated protection against oxidant stress-induced apoptosis in cardiac myocytes.. Circ Res 2001 Jun 22;88(12):1239-46.
                pubmed: 11420299doi: 10.1161/hh1201.091794google scholar: lookup
              40. Xin X, Hou YT, Li L, Schmiedlin-Ren P, Christman GM, Cheng HL, Bitar KN, Zimmermann EM. IGF-I increases IGFBP-5 and collagen alpha1(I) mRNAs by the MAPK pathway in rat intestinal smooth muscle cells.. Am J Physiol Gastrointest Liver Physiol 2004 May;286(5):G777-83.
                pubmed: 15068962doi: 10.1152/ajpgi.00293.2003google scholar: lookup
              41. Veraldi KL, Gibson BT, Yasuoka H, Myerburg MM, Kelly EA, Balzar S, Jarjour NN, Pilewski JM, Wenzel SE, Feghali-Bostwick CA. Role of insulin-like growth factor binding protein-3 in allergic airway remodeling.. Am J Respir Crit Care Med 2009 Oct 1;180(7):611-7.
                pmc: PMC2753789pubmed: 19608721doi: 10.1164/rccm.200810-1555OCgoogle scholar: lookup
              42. McWhinnie R, Pechkovsky DV, Zhou D, Lane D, Halayko AJ, Knight DA, Bai TR. Endothelin-1 induces hypertrophy and inhibits apoptosis in human airway smooth muscle cells.. Am J Physiol Lung Cell Mol Physiol 2007 Jan;292(1):L278-86.
                pubmed: 16920889doi: 10.1152/ajplung.00111.2006google scholar: lookup
              43. Crabtree GR. Calcium, calcineurin, and the control of transcription.. J Biol Chem 2001 Jan 26;276(4):2313-6.
                pubmed: 11096121doi: 10.1074/jbc.R000024200google scholar: lookup
              44. Wu H, Peisley A, Graef IA, Crabtree GR. NFAT signaling and the invention of vertebrates.. Trends Cell Biol 2007 Jun;17(6):251-60.
                pubmed: 17493814doi: 10.1016/j.tcb.2007.04.006google scholar: lookup
              45. Rao A, Luo C, Hogan PG. Transcription factors of the NFAT family: regulation and function.. Annu Rev Immunol 1997;15:707-47.
                pubmed: 9143705doi: 10.1146/annurev.immunol.15.1.707google scholar: lookup
              46. Nozaki K, Tomizawa K, Yokoyama T, Kumon H, Matsui H. Calcineurin mediates bladder smooth muscle hypertrophy after bladder outlet obstruction.. J Urol 2003 Nov;170(5):2077-81.
                pubmed: 14532857doi: 10.1097/01.ju.0000081460.23737.63google scholar: lookup
              47. Balakumar P, Jagadeesh G. Multifarious molecular signaling cascades of cardiac hypertrophy: can the muddy waters be cleared?. Pharmacol Res 2010 Nov;62(5):365-83.
                pubmed: 20643208doi: 10.1016/j.phrs.2010.07.003google scholar: lookup
              48. Clement MR, Delaney DP, Austin JC, Sliwoski J, Hii GC, Canning DA, DiSanto ME, Chacko SK, Zderic SA. Activation of the calcineurin pathway is associated with detrusor decompensation: a potential therapeutic target.. J Urol 2006 Sep;176(3):1225-9.
                pubmed: 16890730doi: 10.1016/j.juro.2006.04.027google scholar: lookup
              49. Léguillette R, Laviolette M, Bergeron C, Zitouni N, Kogut P, Solway J, Kachmar L, Hamid Q, Lauzon AM. Myosin, transgelin, and myosin light chain kinase: expression and function in asthma.. Am J Respir Crit Care Med 2009 Feb 1;179(3):194-204.
                pmc: PMC2633053pubmed: 19011151doi: 10.1164/rccm.200609-1367OCgoogle scholar: lookup
              50. Trakada G, Tsourapis S, Marangos M, Spiropoulos K. Arterial and bronchoalveolar lavage fluid endothelin-1 concentration in asthma.. Respir Med 2000 Oct;94(10):992-6.
                pubmed: 11059954doi: 10.1053/rmed.2000.0890google scholar: lookup
              51. Zhu G, Carlsen K, Carlsen KH, Lenney W, Silverman M, Whyte MK, Hosking L, Helms P, Roses AD, Hay DW, Barnes MR, Anderson WH, Pillai SG. Polymorphisms in the endothelin-1 (EDN1) are associated with asthma in two populations.. Genes Immun 2008 Jan;9(1):23-9.
                pubmed: 17960156doi: 10.1038/sj.gene.6364441google scholar: lookup
              52. Costa LR, Eades SC, Venugopal CS, Moore RM. Plasma and pulmonary fluid endothelin in horses with seasonal recurrent airway obstruction.. J Vet Intern Med 2009 Nov-Dec;23(6):1239-46.
                pubmed: 19761476doi: 10.1111/j.1939-1676.2009.0385.xgoogle scholar: lookup
              53. Bao Y, Li R, Jiang J, Cai B, Gao J, Le K, Zhang F, Chen S, Liu P. Activation of peroxisome proliferator-activated receptor gamma inhibits endothelin-1-induced cardiac hypertrophy via the calcineurin/NFAT signaling pathway.. Mol Cell Biochem 2008 Oct;317(1-2):189-96.
                pubmed: 18600431doi: 10.1007/s11010-008-9848-8google scholar: lookup
              54. Dai Z, Wu F, Yeung EW, Li Y. IGF-IEc expression, regulation and biological function in different tissues.. Growth Horm IGF Res 2010 Aug;20(4):275-81.
                pubmed: 20494600doi: 10.1016/j.ghir.2010.03.005google scholar: lookup
              55. Kawaguchi M, Fujita J, Kokubu F, Ohara G, Huang SK, Matsukura S, Ishii Y, Adachi M, Satoh H, Hizawa N. Induction of insulin-like growth factor-I by interleukin-17F in bronchial epithelial cells.. Clin Exp Allergy 2010 Jul;40(7):1036-43.
                pubmed: 20642578doi: 10.1111/j.1365-2222.2010.03527.xgoogle scholar: lookup
              56. Chetty A, Cao GJ, Nielsen HC. Insulin-like Growth Factor-I signaling mechanisms, type I collagen and alpha smooth muscle actin in human fetal lung fibroblasts.. Pediatr Res 2006 Oct;60(4):389-94.
                pubmed: 16940243doi: 10.1203/01.pdr.0000238257.15502.f4google scholar: lookup
              57. Hayashi K, Takahashi M, Kimura K, Nishida W, Saga H, Sobue K. Changes in the balance of phosphoinositide 3-kinase/protein kinase B (Akt) and the mitogen-activated protein kinases (ERK/p38MAPK) determine a phenotype of visceral and vascular smooth muscle cells.. J Cell Biol 1999 May 17;145(4):727-40.
                pmc: PMC2133182pubmed: 10330402doi: 10.1083/jcb.145.4.727google scholar: lookup
              58. Ohkawa Y, Hayashi K, Sobue K. Calcineurin-mediated pathway involved in the differentiated phenotype of smooth muscle cells.. Biochem Biophys Res Commun 2003 Jan 31;301(1):78-83.
                pubmed: 12535643doi: 10.1016/s0006-291x(02)02965-0google scholar: lookup
              59. Yamashita N, Tashimo H, Ishida H, Matsuo Y, Arai H, Nagase H, Adachi T, Ohta K. Role of insulin-like growth factor-I in allergen-induced airway inflammation and remodeling.. Cell Immunol 2005 Jun;235(2):85-91.
                pubmed: 16168397doi: 10.1016/j.cellimm.2005.07.006google scholar: lookup
              60. Benayoun L, Druilhe A, Dombret MC, Aubier M, Pretolani M. Airway structural alterations selectively associated with severe asthma.. Am J Respir Crit Care Med 2003 May 15;167(10):1360-8.
                pubmed: 12531777doi: 10.1164/rccm.200209-1030OCgoogle scholar: lookup
              61. Dutsch-Wicherek M. RCAS1, MT, and vimentin as potential markers of tumor microenvironment remodeling.. Am J Reprod Immunol 2010 Mar 1;63(3):181-8.
                pubmed: 20085563doi: 10.1111/j.1600-0897.2009.00803.xgoogle scholar: lookup
              62. Pettipher R, Hansel TT, Armer R. Antagonism of the prostaglandin D2 receptors DP1 and CRTH2 as an approach to treat allergic diseases.. Nat Rev Drug Discov 2007 Apr;6(4):313-25.
                pubmed: 17396136doi: 10.1038/nrd2266google scholar: lookup
              63. Winkler GS, Mulder KW, Bardwell VJ, Kalkhoven E, Timmers HT. Human Ccr4-Not complex is a ligand-dependent repressor of nuclear receptor-mediated transcription.. EMBO J 2006 Jul 12;25(13):3089-99.
                pmc: PMC1500986pubmed: 16778766doi: 10.1038/sj.emboj.7601194google scholar: lookup
              64. Wenzel SE, Schwartz LB, Langmack EL, Halliday JL, Trudeau JB, Gibbs RL, Chu HW. Evidence that severe asthma can be divided pathologically into two inflammatory subtypes with distinct physiologic and clinical characteristics.. Am J Respir Crit Care Med 1999 Sep;160(3):1001-8.
                pubmed: 10471631doi: 10.1164/ajrccm.160.3.9812110google scholar: lookup
              65. Watanabe S, Yamasaki A, Hashimoto K, Shigeoka Y, Chikumi H, Hasegawa Y, Sumikawa T, Takata M, Okazaki R, Watanabe M, Yokogawa T, Yamamura M, Hayabuchi T, Gerthoffer WT, Halayko AJ, Shimizu E. Expression of functional leukotriene B4 receptors on human airway smooth muscle cells.. J Allergy Clin Immunol 2009 Jul;124(1):59-65.e1-3.
                pmc: PMC4301732pubmed: 19477492doi: 10.1016/j.jaci.2009.03.024google scholar: lookup
              66. Luster AD, Tager AM. T-cell trafficking in asthma: lipid mediators grease the way.. Nat Rev Immunol 2004 Sep;4(9):711-24.
                pubmed: 15343370doi: 10.1038/nri1438google scholar: lookup
              67. Montuschi P, Barnes PJ. Exhaled leukotrienes and prostaglandins in asthma.. J Allergy Clin Immunol 2002 Apr;109(4):615-20.
                pubmed: 11941309doi: 10.1067/mai.2002.122461google scholar: lookup
              68. Rao NL, Riley JP, Banie H, Xue X, Sun B, Crawford S, Lundeen KA, Yu F, Karlsson L, Fourie AM, Dunford PJ. Leukotriene A(4) hydrolase inhibition attenuates allergic airway inflammation and hyperresponsiveness.. Am J Respir Crit Care Med 2010 May 1;181(9):899-907.
                pubmed: 20110560doi: 10.1164/rccm.200807-1158OCgoogle scholar: lookup
              69. Snelgrove RJ, Jackson PL, Hardison MT, Noerager BD, Kinloch A, Gaggar A, Shastry S, Rowe SM, Shim YM, Hussell T, Blalock JE. A critical role for LTA4H in limiting chronic pulmonary neutrophilic inflammation.. Science 2010 Oct 1;330(6000):90-4.
                pmc: PMC3072752pubmed: 20813919doi: 10.1126/science.1190594google scholar: lookup
              70. Ulven T, Kostenis E. Novel CRTH2 antagonists: a review of patents from 2006 to 2009.. Expert Opin Ther Pat 2010 Nov;20(11):1505-30.
                pubmed: 20946089doi: 10.1517/13543776.2010.525506google scholar: lookup

              Citations

              This article has been cited 6 times.
              1. Mainguy-Seers S, Beaudry F, Fernandez-Prada C, Martin JG, Lavoie JP. Neutrophil Extracellular Vesicles and Airway Smooth Muscle Proliferation in the Natural Model of Severe Asthma in Horses.. Cells 2022 Oct 24;11(21).
                doi: 10.3390/cells11213347pubmed: 36359743google scholar: lookup
              2. Kreus M, Lehtonen S, Hinttala R, Salonen J, Porvari K, Kaarteenaho R. NHLRC2 expression is increased in idiopathic pulmonary fibrosis.. Respir Res 2022 Aug 13;23(1):206.
                doi: 10.1186/s12931-022-02129-zpubmed: 35964085google scholar: lookup
              3. Sheats MK, Davis KU, Poole JA. Comparative Review of Asthma in Farmers and Horses.. Curr Allergy Asthma Rep 2019 Oct 10;19(11):50.
                doi: 10.1007/s11882-019-0882-2pubmed: 31599358google scholar: lookup
              4. Korn A, Miller D, Dong L, Buckles EL, Wagner B, Ainsworth DM. Differential Gene Expression Profiles and Selected Cytokine Protein Analysis of Mediastinal Lymph Nodes of Horses with Chronic Recurrent Airway Obstruction (RAO) Support an Interleukin-17 Immune Response.. PLoS One 2015;10(11):e0142622.
                doi: 10.1371/journal.pone.0142622pubmed: 26561853google scholar: lookup
              5. 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.
                doi: 10.1371/journal.pone.0122011pubmed: 25790166google scholar: lookup
              6. Sobkowicz AD, Gallagher ME, Reid CJ, Crean D, Carrington SD, Irwin JA. Modulation of expression in BEAS-2B airway epithelial cells of α-L-fucosidase A1 and A2 by Th1 and Th2 cytokines, and overexpression of α-L-fucosidase 2.. Mol Cell Biochem 2014 May;390(1-2):101-13.
                doi: 10.1007/s11010-014-1961-2pubmed: 24469468google scholar: lookup
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