{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T13:05:29Z","timestamp":1783083929753,"version":"3.54.6"},"reference-count":87,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T00:00:00Z","timestamp":1763942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre","doi-asserted-by":"publisher","award":["2020\/37\/B\/NZ9\/03355"],"award-info":[{"award-number":["2020\/37\/B\/NZ9\/03355"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Equine endometrosis is a chronic degenerative condition of the endometrium. A hallmark feature of endometrosis is endometrial fibrosis accompanied by degenerative changes in the adjacent tissue structure. Tumor necrosis factor \u03b1 (TNF\u03b1), a pleiotropic cytokine produced by various immune cells, plays a dual role in coordinating immune responses and regulating cell\/tissue homeostasis, making it an important regulator of fibrotic-related disorders. However, the exact role of TNF\u03b1 in the development of equine endometrial fibrosis remains to be discovered and explained. Therefore, the main aim of the current study was to establish the effects of TNF\u03b1 on the equine endometrial fibroblast transcriptome as well as on proliferation and expression of ECM-associated factors in in vitro cultured fibroblasts derived from non-fibrotic equine endometrium. RNA-sequencing revealed changes in the expression of 737 genes (padjusted &lt; 0.05; log2FC \u2265 1.0\/log2FC \u2264 \u22121.0) between untreated and TNF\u03b1-treated equine endometrial fibroblasts. These genes are involved in, i.a., B cell activation, proliferation and differentiation, cell cycle, canonical NF-\u03baB signal transduction, ERK1 and ERK2 cascade, and p53 signaling pathway. Moreover, it was found that TNF\u03b1 increased fibroblast proliferation and affected the expression of metalloproteinases and their tissue inhibitors in mare endometrial fibroblasts. Results of the current study highlight that TNF\u03b1 modulates the expression of genes related to immune cell activation, cell fate, and ECM remodeling in in vitro cultured equine endometrial fibroblasts, suggesting TNF\u03b1 contribution in development of fibrosis in the mare endometrium. Since the current study provides mechanistic insight into TNF\u03b1 action, these findings provide a foundation for future research aimed at targeting TNF\u03b1-mediated pathways as potential therapeutic strategies to mitigate equine endometrial fibrosis progression.<\/jats:p>","DOI":"10.3390\/ijms262311344","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T11:47:22Z","timestamp":1763984842000},"page":"11344","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptomic Insights into Tumor Necrosis Factor \u03b1\u2019s Role in the Fibrosis-Related Processes of Equine Endometrial Fibroblasts"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3188-792X","authenticated-orcid":false,"given":"Agnieszka","family":"Sadowska","sequence":"first","affiliation":[{"name":"Team of Molecular Basis of Equine Reproduction, Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, 10-683 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0380-0156","authenticated-orcid":false,"given":"Tomasz","family":"Molcan","sequence":"additional","affiliation":[{"name":"Molecular Biology Laboratory, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-683 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9357-4844","authenticated-orcid":false,"given":"Magda","family":"S\u0142yszewska","sequence":"additional","affiliation":[{"name":"Team of Molecular Basis of Equine Reproduction, Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, 10-683 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9537-3560","authenticated-orcid":false,"given":"Dariusz J.","family":"Skarzynski","sequence":"additional","affiliation":[{"name":"Team of Reproductive Pathology and Translational Medicine, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-683 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0622-6513","authenticated-orcid":false,"given":"Gra\u00e7a","family":"Ferreira-Dias","sequence":"additional","affiliation":[{"name":"CIISA\u2014Center for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, 1300-477 Lisbon, Portugal"},{"name":"Associate Laboratory for Animal and Veterinary Sciences (AL4AnimalS), 1300-477 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Sz\u00f3stek-Mioduchowska","sequence":"additional","affiliation":[{"name":"Team of Molecular Basis of Equine Reproduction, Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, 10-683 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.anireprosci.2008.03.019","article-title":"The equine endometrosis: New insights into the pathogenesis","volume":"111","author":"Hoffmann","year":"2009","journal-title":"Anim. 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