FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Cell and tissue research2026; 403(2); 25; doi: 10.1007/s00441-026-04049-6

Interleukin-4 changes the transcriptome, ECM-associated components and function of mare endometrial fibroblast: Insights from healthy and fibrotic cells.

Abstract: Fibrosis remains incompletely understood, particularly in terms of how immune mediators shape stromal programs. We used a spontaneous large‑animal model-endometrosis (equine endometrial fibrosis) to define how interleukin‑4 (IL‑4) reprograms fibroblasts from healthy and fibrotic endometrium. Primary fibroblasts were exposed to IL‑4 (10 ng/mL) for 48 or 96 h. At 48 h, bulk transcriptomes revealed 1307 differentially expressed genes (DEGs; 648 up, 659 down) and 1271 DEGs (645 up, 626 down) in fibroblasts derived from endometria without or with endometrosis, respectively. Enrichment analyses implicated cellular metabolism, extracellular matrix (ECM) organization and remodeling, and signaling pathways commonly linked to fibrogenesis. IL‑4 also affected the long non‑coding RNA (lncRNA) expression, with 143 and 135 differentially expressed lncRNAs in fibroblasts derived from healthy or fibrotic endometria, respectively; linking these lncRNAs to DEGs involved in inflammation, ECM organization, and cytokine signaling. Moreover, IL‑4 increased proliferation and viability in fibroblasts derived from healthy or fibrotic endometria, while selectively reducing migration in fibroblasts derived from endometria without fibrosis after 96 h. IL‑4 further altered mRNA expression, protein abundance, and gelatinolytic activity of matrix metalloproteinases in a manner contingent on the fibrosis status of the tissue of origin, indicating stage‑dependent control of ECM turnover. Collectively, these data identify IL‑4 as a potent modulator of fibroblast function in a spontaneous large‑animal fibrosis model, revealing fibrosis stage‑dependent responses.
© 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Get Full Text
Publication Date: 2026-02-23 PubMed ID: 41729313PubMed Central: 3302189DOI: 10.1007/s00441-026-04049-6Google 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.
LinkedInCopy
  • 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.

Overview

  • This study investigates how interleukin-4 (IL-4), an immune signaling molecule, influences the behavior and gene expression of fibroblasts in the mare’s endometrium, both in healthy tissue and in tissue affected by fibrosis (endometrosis).
  • The research reveals that IL-4 notably changes gene activity, extracellular matrix-related components, and the functional characteristics of these fibroblasts in a way that depends on whether the tissue is fibrotic or not.

Background and Objective

  • Fibrosis is a process where excessive connective tissue builds up, impairing normal tissue function; it remains poorly understood, especially how immune factors such as IL-4 influence stromal (connective) cells.
  • The mare endometrium provides a spontaneous large-animal model of fibrosis called endometrosis, allowing study in a relevant biological context.
  • The researchers aimed to clarify how IL-4 affects fibroblast gene expression (transcriptome), extracellular matrix (ECM) components, and cellular functions in healthy versus fibrotic endometrial fibroblasts.

Methodology

  • Primary fibroblasts were isolated from mare endometrial tissue, both from healthy samples and from those with fibrotic changes (endometrosis).
  • Cells were treated with IL-4 at a concentration of 10 ng/mL, for two durations: 48 hours and 96 hours.
  • Bulk RNA sequencing was performed at 48 hours to identify differentially expressed genes (DEGs) between treated and untreated cells.
  • Functional assays measured fibroblast proliferation, viability, and migration.
  • Protein analysis assessed matrix metalloproteinases (MMPs) abundance, and enzymatic activity assays focused on gelatinolytic activity, indicative of ECM remodeling capacity.

Key Findings: Transcriptomic Changes

  • At 48 hours, IL-4 treatment induced large-scale gene expression changes:
    • In fibroblasts from healthy endometrium: 1307 DEGs (648 upregulated, 659 downregulated).
    • In fibroblasts from fibrotic tissue: 1271 DEGs (645 upregulated, 626 downregulated).
  • Gene enrichment analysis showed affected pathways related to:
    • Cellular metabolism.
    • Extracellular matrix organization and remodeling.
    • Fibrosis-associated signaling pathways.
  • Long non-coding RNAs (lncRNAs), which regulate gene expression, were also altered by IL-4:
    • 143 lncRNAs differentially expressed in healthy fibroblasts.
    • 135 in fibrotic fibroblasts.
    • Many of these lncRNAs linked to genes involved in inflammation, ECM organization, and cytokine signaling.

Functional Effects of IL-4 on Fibroblasts

  • IL-4 increased both proliferation (cell growth) and viability in fibroblasts from healthy and fibrotic tissues.
  • Migration behavior was selectively reduced by IL-4 in fibroblasts from healthy endometrium after 96 hours, but not in fibrotic fibroblasts.

Regulation of ECM Remodeling and MMP Activity

  • Matrix metalloproteinases (MMPs) are enzymes that degrade ECM components, playing a key role in ECM turnover and fibrosis.
  • IL-4 modified:
    • MMP mRNA expression levels.
    • Protein abundance of MMPs.
    • Gelatinolytic enzymatic activity of MMPs.
  • These changes were dependent on whether the fibroblasts originated from healthy or fibrotic tissues, indicating IL-4’s role is stage-dependent in controlling ECM dynamics during fibrosis progression.

Conclusions and Implications

  • IL-4 acts as a strong modulator of fibroblast behavior and gene expression in the mare endometrium.
  • The cytokine’s effects vary depending on whether the fibroblasts come from healthy or fibrotic tissue, highlighting different cellular states or stages of fibrosis.
  • This study provides novel insights into immune regulation of fibrosis in a relevant large-animal model, which may help develop strategies to manage or treat fibrosis by targeting IL-4 pathways.

Cite This Article

APA
Wójtowicz A, Sadowska A, Myszczyński K, Molcan T, Kaczmarek MM, Szóstek-Mioduchowska A. (2026). Interleukin-4 changes the transcriptome, ECM-associated components and function of mare endometrial fibroblast: Insights from healthy and fibrotic cells. Cell Tissue Res, 403(2), 25. https://doi.org/10.1007/s00441-026-04049-6

Publication

Cell and tissue research
ISSN: 1432-0878
NlmUniqueID: 0417625
Country: Germany
Language: English
Volume: 403
Issue: 2
PII: 25

Researcher Affiliations

Wójtowicz, Anna
  • Team of Molecular Basis of Equine Reproduction, InLife Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
Sadowska, Agnieszka
  • Team of Molecular Basis of Equine Reproduction, InLife Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
Myszczyński, Kamil
  • Molecular Biology Laboratory, InLife Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
  • Computational Biology Laboratory, InLife Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
Molcan, Tomasz
  • Molecular Biology Laboratory, InLife Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
  • Computational Biology Laboratory, InLife Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
Kaczmarek, Monika M
  • Team of Programming of Fertility and Development, InLife Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
Szóstek-Mioduchowska, Anna
  • Team of Molecular Basis of Equine Reproduction, InLife Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland. a.szostek-mioduchowska@pan.olsztyn.pl.

MeSH Terms

  • Animals
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Fibroblasts / drug effects
  • Endometrium / pathology
  • Endometrium / metabolism
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / drug effects
  • Transcriptome / drug effects
  • Transcriptome / genetics
  • Fibrosis
  • Interleukin-4 / pharmacology
  • Horses
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • Cell Proliferation / drug effects
  • Cell Movement / drug effects
  • Gene Expression Profiling

Conflict of Interest Statement

Declarations. Ethics approval: This study used mare endometrial tissue obtained post-mortem from mares at a commercial slaughterhouse, where the animals were processed solely for meat production. As the samples were collected after death from non-experimental animals, no ethical approval was required. Competing interests: The authors declare no competing interests.

References

This article includes 59 references
  1. Allen JE. IL-4 and IL-13: regulators and effectors of wound repair.. Annu Rev Immunol 41:229–254.
    pubmed: 36737597doi: 10.1146/annurev-immunol-101921-041206google scholar: lookup
  2. Andersen CL, Jensen JL, Orntoft 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 64:5245–5250.
    pubmed: 15289330doi: 10.1158/0008-5472.CAN-04-0496google scholar: lookup
  3. Aoudjehane L, Pissaia AJ, Scatton O, Podevin P, Massault PP, Chouzenoux S, Soubrane O, Calmus Y, Conti F. Interleukin-4 induces the activation and collagen production of cultured human intrahepatic fibroblasts via the STAT-6 pathway.. Lab Invest 88:973–985.
    pubmed: 18626468doi: 10.1038/labinvest.2008.61google scholar: lookup
  4. Arpino V, Brock M, Gill SE. The role of TIMPs in regulation of extracellular matrix proteolysis.. Matrix Biol 44–46:247–254.
    pubmed: 25805621doi: 10.1016/j.matbio.2015.03.005google scholar: lookup
  5. Arthur MJ, Iredale JP, Mann DA. Tissue inhibitors of metalloproteinases: role in liver fibrosis and alcoholic liver disease.. Alcohol Clin Exp Res 23:940–943.
    pubmed: 10371419
  6. Barron L, Wynn TA. Fibrosis is regulated by Th2 and Th17 responses and by dynamic interactions between fibroblasts and macrophages.. Am J Physiol Gastrointest Liver Physiol 300:G723–G728.
    pubmed: 21292997pmc: 3302189doi: 10.1152/ajpgi.00414.2010google scholar: lookup
  7. Batsaikhan B, Lu MY, Yeh ML, Huang CI, Huang CF, Lin ZY, Chen SC, Huang JF, Hsieh PH, Chuang WL, Lee JC, Yu ML, Dai CY. Elevated interleukin-4 levels predicted advanced fibrosis in chronic hepatitis C.. J Chin Med Assoc 82:277–281.
    pubmed: 30946707doi: 10.1097/JCMA.0000000000000064google scholar: lookup
  8. Bhattacharya M, Ramachandran P. Immunology of human fibrosis.. Nat Immunol 24:1423–1433.
    pubmed: 37474654doi: 10.1038/s41590-023-01551-9google scholar: lookup
  9. Bracher V, Mathias S, Allen WR. Influence of chronic degenerative endometritis (endometrosis) on placental development in the mare.. Equine Vet J 28:180–188.
    pubmed: 28976715doi: 10.1111/j.2042-3306.1996.tb03771.xgoogle scholar: lookup
  10. Bukowska J, Kopcewicz M, Kur-Piotrowska A, Szostek-Mioduchowska AZ, Walendzik K, Gawronska-Kozak B. Effect of TGFbeta1, TGFbeta3 and keratinocyte conditioned media on functional characteristics of dermal fibroblasts derived from reparative (Balb/c) and regenerative (Foxn1 deficient; nude) mouse models.. Cell Tissue Res 374:149–163.
    pubmed: 29637306pmc: 6132647doi: 10.1007/s00441-018-2836-8google scholar: lookup
  11. Camacho C, Coulouris G, Avagyan V, Ma N, Papadopoulos J, Bealer K, Madden TL. BLAST+: architecture and applications.. BMC Bioinformatics 10:421.
    pubmed: 20003500pmc: 2803857doi: 10.1186/1471-2105-10-421google scholar: lookup
  12. Cui X, Shi E, Li J, Li Y, Qiao Z, Wang Z, Liu M, Tang W, Sun Y, Zhang Y, Xie Y, Zhen J, Wang X, Yi F. GPR87 promotes renal tubulointerstitial fibrosis by accelerating glycolysis and mitochondrial injury.. Free Radic Biol Med 189:58–70.
    pubmed: 35843477doi: 10.1016/j.freeradbiomed.2022.07.004google scholar: lookup
  13. D’Arcy Q, Gharaee-Kermani M, Zhilin-Roth A, Macoska JA. The IL-4/IL-13 signaling axis promotes prostatic fibrosis.. PLoS One 17:e0275064.
    pubmed: 36201508pmc: 9536598doi: 10.1371/journal.pone.0275064google scholar: lookup
  14. Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR. STAR: ultrafast universal RNA-seq aligner.. Bioinformatics 29:15–21.
    pubmed: 23104886doi: 10.1093/bioinformatics/bts635google scholar: lookup
  15. Doucet C, Brouty-Boye D, Pottin-Clemenceau C, Jasmin C, Canonica GW, Azzarone B. IL-4 and IL-13 specifically increase adhesion molecule and inflammatory cytokine expression in human lung fibroblasts.. Int Immunol 10:1421–1433.
    pubmed: 9796908doi: 10.1093/intimm/10.10.1421google scholar: lookup
  16. Flores JM, Rodriguez A, Sanchez J, Gomezcuetara C, Ramiro F. Endometriosis in mares - incidence of histopathological alterations. Reprod Domest Anim 30:61–65.
    doi: 10.1111/j.1439-0531.1995.tb00606.xgoogle scholar: lookup
  17. Giannandrea M, Parks WC. Diverse functions of matrix metalloproteinases during fibrosis. Dis Model Mech 7:193–203.
    pubmed: 24713275pmc: 3917240doi: 10.1242/dmm.012062google scholar: lookup
  18. Gomez DE, Alonso DF, Yoshiji H, Thorgeirsson UP. Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur J Cell Biol 74:111–122.
    pubmed: 9352216
  19. Gu Z. Complex heatmap visualization. Imeta 1:e43.
    pubmed: 38868715pmc: 10989952doi: 10.1002/imt2.43google scholar: lookup
  20. Han S, Liang Y, Ma Q, Xu Y, Zhang Y, Du W, Wang C, Li Y. Lncfinder: an integrated platform for long non-coding RNA identification utilizing sequence intrinsic composition, structural information and physicochemical property. Brief Bioinform 20:2009–2027.
    pubmed: 30084867pmc: 6954391doi: 10.1093/bib/bby065google scholar: lookup
  21. Henderson J, O’Reilly S. The emerging role of metabolism in fibrosis. Trends Endocrinol Metab 32:639–653.
    pubmed: 34024695doi: 10.1016/j.tem.2021.05.003google scholar: lookup
  22. Henderson NC, Rieder F, Wynn TA. Fibrosis: from mechanisms to medicines. Nature 587:555–566.
    pubmed: 33239795pmc: 8034822doi: 10.1038/s41586-020-2938-9google scholar: lookup
  23. Hofacker IL, Fontana W, Stadler PF, Bonhoeffer LS, Tacker M, Schuster P. Fast folding and comparison of RNA secondary structures. Monatsh Chem 125:167–188.
    doi: 10.1007/BF00818163google scholar: lookup
  24. Hoffmann C, Ellenberger C, Mattos RC, Aupperle H, Dhein S, Stief B, Schoon HA. The equine endometrosis: new insights into the pathogenesis. Anim Reprod Sci 111:261–278.
    pubmed: 18468817doi: 10.1016/j.anireprosci.2008.03.019google scholar: lookup
  25. Hong KH, Cho ML, Min SY, Shin YJ, Yoo SA, Choi JJ, Kim WU, Song SW, Cho CS. Effect of interleukin-4 on vascular endothelial growth factor production in rheumatoid synovial fibroblasts. Clin Exp Immunol 147:573–579.
    pubmed: 17302909pmc: 1810499doi: 10.1111/j.1365-2249.2006.03295.xgoogle scholar: lookup
  26. Huaux F, Liu T, McGarry B, Ullenbruch M, Phan SH. Dual roles of IL-4 in lung injury and fibrosis. J Immunol 170:2083–2092.
    pubmed: 12574379doi: 10.4049/jimmunol.170.4.2083google scholar: lookup
  27. Hwang S, Chung KW. Targeting fatty acid metabolism for fibrotic disorders. Arch Pharm Res 44:839–856.
    pubmed: 34664210doi: 10.1007/s12272-021-01352-4google scholar: lookup
  28. Kenney RM, Doig PA. Equine endometrial biopsy. In: Morrow DA (ed) Current therapy in theriogenology, pp 723–29.
  29. Kotlowska M, Kowalski R, Glogowski J, Jankowski J, Ciereszko A. Gelatinases and serine proteinase inhibitors of seminal plasma and the reproductive tract of turkey (Meleagris gallopavo). Theriogenology 63:1667–1681.
    pubmed: 15763110doi: 10.1016/j.theriogenology.2004.07.020google scholar: lookup
  30. Lehmann J, Ellenberger C, Hoffmann C, Bazer FW, Klug J, Allen WR, Sieme H, Schoon HA. Morpho-functional studies regarding the fertility prognosis of mares suffering from equine endometrosis. Theriogenology 76:1326–1336.
    pubmed: 21855986doi: 10.1016/j.theriogenology.2011.06.001google scholar: lookup
  31. Liu X, Conner H, Kobayashi T, Abe S, Fang Q, Wen FQ, Rennard SI. Synergetic effect of interleukin-4 and transforming growth factor-beta1 on type I collagen gel contraction and degradation by HFL-1 cells: implication in tissue remodeling. Chest 123:427S-S428.
    pubmed: 12629015doi: 10.1378/chest.123.3_suppl.427Sgoogle scholar: lookup
  32. Lorenz R, Bernhart SH, Honer Zu Siederdissen C, Tafer H, Flamm C, Stadler PF, Hofacker IL. ViennaRNA Package 2.0. Algorithms Mol Biol 6:26.
    pubmed: 22115189pmc: 3319429doi: 10.1186/1748-7188-6-26google scholar: lookup
  33. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15:550.
    pubmed: 25516281pmc: 4302049doi: 10.1186/s13059-014-0550-8google scholar: lookup
  34. Lupher ML Jr., Gallatin WM. Regulation of fibrosis by the immune system. Adv Immunol 89:245–288.
  35. Miki H, Manresa MC. Novel fibroblast phenotypes in homeostasis and chronic inflammation: from functions to potential regulators. J Physiol 601:2273–2291.
    pubmed: 37062932doi: 10.1113/JP284620google scholar: lookup
  36. Padmanabhan J, Maan ZN, Kwon SH, Kosaraju R, Bonham CA, Gurtner GC. In vivo models for the study of fibrosis. Adv Wound Care 8:645–654.
    doi: 10.1089/wound.2018.0909google scholar: lookup
  37. Peng H, Sarwar Z, Yang XP, Peterson EL, Xu J, Janic B, Rhaleb N, Carretero OA, Rhaleb NE. Profibrotic role for interleukin-4 in cardiac remodeling and dysfunction. Hypertension 66:582–589.
    pubmed: 26195478pmc: 4685692doi: 10.1161/HYPERTENSIONAHA.115.05627google scholar: lookup
  38. Pertea G, Pertea M. GFF utilities: GffRead and GffCompare. F1000Res .
    doi: 10.12688/f1000research.23297.2pubmed: 32489650pmc: 7222033google scholar: lookup
  39. Pertea M, Pertea GM, Antonescu CM, Chang TC, Mendell JT, Salzberg SL. StringTie enables improved reconstruction of a transcriptome from RNA-seq reads. Nat Biotechnol 33:290–295.
    pubmed: 25690850pmc: 4643835doi: 10.1038/nbt.3122google scholar: lookup
  40. Rabbani N, Thornalley PJ. Hexokinase-2 glycolytic overload in diabetes and ischemia-reperfusion injury. Trends Endocrinol Metab 30:419–431.
    pubmed: 31221272doi: 10.1016/j.tem.2019.04.011google scholar: lookup
  41. Rosenbloom J, Macarak E, Piera-Velazquez S, Jimenez SA. Human fibrotic diseases: current challenges in fibrosis research. Methods Mol Biol 1627:1–23.
    pubmed: 28836191doi: 10.1007/978-1-4939-7113-8_1google scholar: lookup
  42. Sempowski GD, Beckmann MP, Derdak S, Phipps RP. Subsets of murine lung fibroblasts express membrane-bound and soluble IL-4 receptors. Role of IL-4 in enhancing fibroblast proliferation and collagen synthesis. J Immunol 152:3606–3614.
    pubmed: 7908305doi: 10.4049/jimmunol.152.7.3606google scholar: lookup
  43. Smolgovsky S, Theall B, Wagner N, Alcaide P. Fibroblasts and immune cells: at the crossroad of organ inflammation and fibrosis. Am J Physiol Heart Circ Physiol 326:H303–H316.
    pubmed: 38038714doi: 10.1152/ajpheart.00545.2023google scholar: lookup
  44. Steinke JW, Crouse CD, Bradley D, Hise K, Lynch K, Kountakis SE, Borish L. Characterization of interleukin-4-stimulated nasal polyp fibroblasts. Am J Respir Cell Mol Biol 30:212–219.
    pubmed: 12920052doi: 10.1165/rcmb.2003-0071OCgoogle scholar: lookup
  45. Szóstek-Mioduchowska A, Wójtowicz A, Sadowska A, Moza Jalali B, Slyszewska M, Lukasik K, Gurgul A, Szmatola T, Bugno-Poniewierska M, Ferreira-Dias G, Skarzynski DJ. Transcriptomic profiling of mare endometrium at different stages of endometrosis. Sci Rep 13:16263.
    pubmed: 37758834pmc: 10533846doi: 10.1038/s41598-023-43359-5google scholar: lookup
  46. Tian Y, Duan C, Feng J, Liao J, Yang Y, Sun W. Roles of lipid metabolism and its regulatory mechanism in idiopathic pulmonary fibrosis: a review. Int J Biochem Cell Biol 155:106361.
    pubmed: 36592687doi: 10.1016/j.biocel.2022.106361google scholar: lookup
  47. Ung CY, Onoufriadis A, Parsons M, McGrath JA, Shaw TJ. Metabolic perturbations in fibrosis disease. Int J Biochem Cell Biol 139:106073.
    pubmed: 34461262doi: 10.1016/j.biocel.2021.106073google scholar: lookup
  48. Wang S, Liang Y, Dai C. Metabolic regulation of fibroblast activation and proliferation during organ fibrosis. Kidney Dis (Basel) 8:115–125.
    pubmed: 35527985pmc: 9021660doi: 10.1159/000522417google scholar: lookup
  49. Wen FQ, Kohyama T, Liu X, Zhu YK, Wang H, Kim HJ, Kobayashi T, Abe S, Spurzem JR, Rennard SI. Interleukin-4- and interleukin-13-enhanced transforming growth factor-beta2 production in cultured human bronchial epithelial cells is attenuated by interferon-gamma. Am J Respir Cell Mol Biol 26:484–490.
    pubmed: 11919085doi: 10.1165/ajrcmb.26.4.4784google scholar: lookup
  50. Wickham H. Data analysis. In Hadley Wickham (ed.), ggplot2: Elegant Graphics for Data Analysis (Springer International Publishing: Cham).
  51. Willems M, Olsen C, Caljon B, Vloeberghs V, De Schepper J, Tournaye H, Van Saen D, Goossens E. Transcriptomic differences between fibrotic and non-fibrotic testicular tissue reveal possible key players in Klinefelter syndrome-related testicular fibrosis. Sci Rep 12:21518.
    pubmed: 36513788pmc: 9748020doi: 10.1038/s41598-022-26011-6google scholar: lookup
  52. Witkowski M, Duliban M, Rak A, Profaska-Szymik M, Gurgul A, Arent ZJ, Galuszka A, Kotula-Balak M. Next-generation sequencing analysis discloses genes implicated in equine endometrosis that may lead to tumorigenesis. Theriogenology 189:158–166.
    pubmed: 35760027doi: 10.1016/j.theriogenology.2022.06.015google scholar: lookup
  53. Wu YS, Liang S, Li DY, Wen JH, Tang JX, Liu HF. Cell cycle dysregulation and renal fibrosis. Front Cell Dev Biol 9:714320.
    pubmed: 34900982pmc: 8660570doi: 10.3389/fcell.2021.714320google scholar: lookup
  54. Wynn TA. Fibrotic disease and the T(H)1/T(H)2 paradigm. Nat Rev Immunol 4:583–594.
    pubmed: 15286725pmc: 2702150doi: 10.1038/nri1412google scholar: lookup
  55. Wynn TA, Ramalingam TR. Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat Med 18:1028–1040.
    pubmed: 22772564pmc: 3405917doi: 10.1038/nm.2807google scholar: lookup
  56. Yin X, Choudhury M, Kang JH, Schaefbauer KJ, Jung MY, Andrianifahanana M, Hernandez DM, Leof EB. Hexokinase 2 couples glycolysis with the profibrotic actions of TGF-beta. Sci Signal 12:eaax4067.
  57. Yu G, Wang LG, Han Y, He QY. Clusterprofiler: an R package for comparing biological themes among gene clusters. OMICS 16:284–287.
    pubmed: 22455463pmc: 3339379doi: 10.1089/omi.2011.0118google scholar: lookup
  58. Zhao M, Wang L, Wang M, Zhou S, Lu Y, Cui H, Racanelli AC, Zhang L, Ye T, Ding B, Zhang B, Yang J, Yao Y. Targeting fibrosis, mechanisms and cilinical trials. Signal Transduct Target Ther 7:206.
    pubmed: 35773269pmc: 9247101doi: 10.1038/s41392-022-01070-3google scholar: lookup
  59. Zhao S, Fernald RD. Comprehensive algorithm for quantitative real-time polymerase chain reaction. J Comput Biol 12:1047–64.

Citations

This article has been cited 0 times.
Subscribe to our newsletter
Join 100,129 horse owners like you who receive our email updates on horse health and nutrition.