{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:15:17Z","timestamp":1790766917750,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,22]],"date-time":"2023-11-22T00:00:00Z","timestamp":1700611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Abnormal function and fibrosis of endometrium caused by cows' endometritis pose difficult implantation of embryos and uterine cavity adhesions. 17\u03b2\u2010Estradiol (E2) serves as the most effective aromatized estrogen, and its synthetase and receptors have been detected in the endometrium. Studies have demonstrated the positive role of estrogen in combating pathological fibrosis in diverse diseases. However, it is still unknown whether E2 regulates endometrium fibrosis in bovine endometritis. Herein, we evaluated the expression patterns of transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21), epithelial\u2010mesenchymal transformation (EMT)\u2010related proteins (\u03b1\u2010SMA, vimentin N\u2010cadherin and E\u2010cadherin), cytochrome P450 19A1 (CYP19A1), and G protein\u2010coupled estrogen receptor (GPER) in bovine healthy endometrium and Inflammatory endometrium. Our data showed that the inflamed endometrium presented low CYP19A1 and GPER expression, and significantly higher EMT process versus the normal tissue. Moreover, we established a TGF\u2010\u03b21\u2010induced fibrosis model in BEND cells, and found that E2 inhibited the EMT process of BEND cells in a dose\u2010dependent manner. The anti\u2010fibrotic effect of E2 was blocked by the GPER inhibitor G15, but not the estrogen nuclear receptors (ERs) inhibitor ICI182780. Moreover, the GPER agonist G1 inhibited fibrosis and Smad2\/3 phosphorylation but increased the expression of TGFBR3 in BEND cells. Transfection with <jats:italic>TGFBR3<\/jats:italic> small interfering RNA blocked the effect of G1 on fibrosis of BEND cells and upregulated the expression of P\u2010Smad2\/3. Our in vivo data also showed that E2 and G1 affected uterus fibrosis in mice endometritis model caused by LPS, which was associated with the inhibition of TGFBR3\/Smad2\/3 signaling. In conclusion, our data implied that E2 alleviates the fibrosis of TGF\u2010\u03b21\u2010induced BEND cells, which is associated with the GPER mediation of TGFBR3\/Smad2\/3 signaling.<\/jats:p>","DOI":"10.1002\/jcp.31153","type":"journal-article","created":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T11:03:50Z","timestamp":1700823830000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["17\u03b2\u2010Estradiol mediates TGFBR3\/Smad2\/3 signaling to attenuate the fibrosis of TGF\u2010\u03b21\u2010induced bovine endometrial epithelial cells via GPER"],"prefix":"10.1002","volume":"239","author":[{"given":"Zihao","family":"Fang","sequence":"first","affiliation":[{"name":"Animal Science and Technology College Beijing University of Agriculture Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"Animal Science and Technology College Beijing University of Agriculture Beijing China"},{"name":"Beijing Municipal Changping district Bureau of Agriculture and Rural Affairs Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Duan","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Gansu Agricultural University Lanzhou Gansu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xihui","family":"Sheng","sequence":"additional","affiliation":[{"name":"Animal Science and Technology College Beijing University of Agriculture Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolong","family":"Qi","sequence":"additional","affiliation":[{"name":"Animal Science and Technology College Beijing University of Agriculture Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Xing","sequence":"additional","affiliation":[{"name":"Animal Science and Technology College Beijing University of Agriculture Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingying","family":"Liu","sequence":"additional","affiliation":[{"name":"Animal Science and Technology College Beijing University of Agriculture Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Chang","sequence":"additional","affiliation":[{"name":"Animal Science and Technology College Beijing University of Agriculture Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Guo","sequence":"additional","affiliation":[{"name":"Animal Science and Technology College Beijing University of Agriculture Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5001-7930","authenticated-orcid":false,"given":"Xiangguo","family":"Wang","sequence":"additional","affiliation":[{"name":"Animal Science and Technology College Beijing University of Agriculture Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5790-6645","authenticated-orcid":false,"given":"Longfei","family":"Xiao","sequence":"additional","affiliation":[{"name":"Animal Science and Technology College Beijing University of Agriculture Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.13262"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2010.01.006"},{"key":"e_1_2_8_4_1","first-page":"162","article-title":"Endometrial biopsy in Holstein\u2010Friesian dairy cows. 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