{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T12:36:37Z","timestamp":1777638997880,"version":"3.51.4"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T00:00:00Z","timestamp":1720569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hubei Provincial Natural Science Foundation of China"},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Intrauterine adhesion (IUA) is manifestations of endometrial fibrosis and excessive extracellular matrix deposition. C1q\/tumor necrosis factor-related protein-6 (CTRP6) is a newly identified adiponectin paralog which has been reported to modulate the fibrosis process of several diseases; however, the endometrial fibrosis function of CTRP6 remains unknown. Our study aimed to assess the role of CTRP6 in endometrial fibrosis and further explore the underlying mechanism. Here, we found that the expression of CTRP6 was downregulated in the endometrial tissues of IUA. In vitro experiments demonstrated the reduced level of CTRP6 in facilitated transforming growth factor-\u03b21 (TGF-\u03b21)-induced human endometrial stromal cells (HESCs). In addition, CTRP6 inhibited the expression of \u03b1-smooth muscle actin (\u03b1-SMA) and collagen I in TGF-\u03b21-treated HESCs. Mechanistically, CTRP6 activated the AMP-activated protein kinase (AMPK) and protein kinase B (AKT) pathway in HESCs, and AMPK inhibitor (AraA) or PI3K inhibitor (LY294002) pretreatment abolished the protective effect of CTRP6 on TGF-\u03b21-induced fibrosis. CTRP6 markedly decreased TGF-\u03b21-induced Smad3 phosphorylation and nuclear translocation, and AMPK or AKT inhibition reversed these effects. Notably, CTRP6-overexpressing treatment alleviated the fibrosis of endometrium in vivo. Therefore, CTRP6 ameliorates endometrial fibrosis, among which AMPK and AKT are essential for the anti-fibrotic effect of CTRP6 via the Smad3 pathway. Taken together, CTRP6 may be a potential therapeutic target for the treatment of intrauterine adhesion.<\/jats:p>","DOI":"10.1093\/biolre\/ioae016","type":"journal-article","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T15:29:05Z","timestamp":1720625345000},"page":"322-331","source":"Crossref","is-referenced-by-count":7,"title":["CTRP6 alleviates endometrial fibrosis by regulating Smad3 pathway in intrauterine adhesion"],"prefix":"10.1093","volume":"111","author":[{"given":"Sisi","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behavior , Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China"},{"name":"Reproductive Medical Center , Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinli","family":"Ding","sequence":"additional","affiliation":[{"name":"Reproductive Medical Center , Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zehao","family":"Wang","sequence":"additional","affiliation":[{"name":"Reproductive Medical Center , Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Reproductive Medical Center , Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Xu","sequence":"additional","affiliation":[{"name":"Renmin Hospital of Wuhan University Department of Otolaryngology-Head and Neck Surgery, , Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yifan","family":"Jia","sequence":"additional","affiliation":[{"name":"Renmin Hospital of Wuhan University Department of Pain, , Wuhan, Hubei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[{"name":"Reproductive Medical Center , Renmin Hospital of Wuhan University and Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Radiation and Medical Oncology, Hubei Key Laboratory of Tumor Biological Behavior , Hubei Cancer Clinical Study Center, Zhongnan Hospital of Wuhan University, Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,7,10]]},"reference":[{"key":"2024081605155084000_ref1","first-page":"137","article-title":"Endometrial stem\/progenitor cells: the first 10 years","volume":"22","author":"Gargett","year":"2016","journal-title":"Hum Reprod Update"},{"key":"2024081605155084000_ref2","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1093\/humupd\/dmt045","article-title":"Systematic review and meta-analysis of intrauterine adhesions after miscarriage: prevalence, risk factors and long-term reproductive outcome","volume":"20","author":"Hooker","year":"2014","journal-title":"Hum Reprod Update"},{"key":"2024081605155084000_ref3","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1111\/1471-0528.13353","article-title":"The influence of the location and extent of intrauterine adhesions on recurrence 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