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Transforming growth factor beta 1 (TGF-\u03b21) promotes fibrosis, while milk fat globule EGF and factor V\/VIII domain containing (MFGE8) primarily exerts antifibrotic effects. We used in situ hybridization analysis (ISH) to investigate\n                    <jats:italic>MFGE8<\/jats:italic>\n                    ,\n                    <jats:italic>TGFB1<\/jats:italic>\n                    and its downstream effectors cellular communication network factor 2 (\n                    <jats:italic>CCN2<\/jats:italic>\n                    ) and transgelin (\n                    <jats:italic>TAGLN<\/jats:italic>\n                    ) in equine endometrial fibrosis. Additionally, transcriptional effects of TGF-\u03b21 and MFGE8 on equine endometrial fibroblasts in vitro were investigated by single cell sequencing. Fibrotic areas overexpressing\n                    <jats:italic>TGFB1<\/jats:italic>\n                    displayed increased\n                    <jats:italic>CCN2<\/jats:italic>\n                    and\n                    <jats:italic>TAGLN<\/jats:italic>\n                    expression. The vast majority of glandular areas overexpressing\n                    <jats:italic>MFGE8<\/jats:italic>\n                    were affected by fibrosis, confirming its relevance in equine endometrial fibrosis. Single cell sequencing following TGF-\u03b21 exposure of fibroblasts confirmed its profibrotic effects. MFGE8 treatment effects were subtler, including decreased profibrotic leukemia inhibitory factor expression and an upregulation of interferon alpha and beta signaling in a subset of cells. In a fibroblast subpopulation, upregulation of phosphatase and tensin homolog signaling, indicated an antifibrotic effect of MFGE8. In conclusion, our study reaffirms the profibrotic effects of TGF-\u03b21 and highlights MFGE8 as a novel player in equine endometrial fibrosis with our results suggesting an antifibrotic effect of MFGE8.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-46595-7","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T10:23:58Z","timestamp":1775730238000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Milk fat globule EGF and factor V\/VIII domain containing (MFGE8) as a novel player in equine endometrial fibrosis"],"prefix":"10.1038","volume":"16","author":[{"given":"Elena","family":"zu Klampen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregor","family":"Neufeld","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Klein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"46595_CR1","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1111\/j.2042-3306.1991.tb02752.x","volume":"23","author":"SW Ricketts","year":"1991","unstructured":"Ricketts, S. 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