{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:55:54Z","timestamp":1789545354008,"version":"build-2803163510"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Sichuan Science and Technology Program","award":["2022NSFSC1357"],"award-info":[{"award-number":["2022NSFSC1357"]}]},{"name":"Nanchong City-School Science and Technology Strategic Cooperation Project","award":["19SXHZ0293"],"award-info":[{"award-number":["19SXHZ0293"]}]},{"name":"Doctoral Initiation Fund Project","award":["CBY21-QD23"],"award-info":[{"award-number":["CBY21-QD23"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Abnormal autophagy and the transforming growth factor-\u03b2 (TGF\u03b2)\u2013SMAD3\/7 signaling pathway play an important role in the development of intrauterine adhesions (IUAs); however, the exact underlying mechanisms remain unclear. In this study, we used IUA patient tissue and SMAD7 conditional knockout mice to detect whether SMAD7 effected IUA via regulation of autophagy and the TGF\u03b2\u2013SMAD3 signaling pathway. We applied a combination of techniques for the detection of p-SMAD3, SMAD7, autophagy and fibrosis-related proteins, autophagic flux, and analysis of the SMAD3 binding site. Endometrial tissue of patients with IUA exhibited lower expression levels of SMAD7. In endometrial stromal cells, silencing of SMAD7 inhibited autophagic flux, whereas overexpressed SMAD7 promoted autophagic flux. This SMAD7-mediated autophagic flux regulates the stromal\u2013myofibroblast transition, and these phenotypes were regulated by the TGF\u03b2\u2013SMAD3 signaling pathway. SMAD3 directly binds to the 3\u02b9-untranslated region of transcription factor EB (TFEB) and inhibits its transcription. SMAD7 promoted autophagic flux by inhibiting SMAD3, thereby promoting the expression of TFEB. In SMAD7 conditional knockout mice, the endometria showed a fibrotic phenotype. Simultaneously, autophagic flux was inhibited. On administering the autophagy activator rapamycin, this endometrial fibrosis phenotype was partially reversed. The loss of SMAD7 promotes endometrial fibrosis by inhibiting autophagic flux via the TGF\u03b2\u2013SMAD3 pathway. Therefore, this study reveals a potential therapeutic target for IUA.<\/jats:p>","DOI":"10.1093\/molehr\/gaae036","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T14:42:11Z","timestamp":1729089731000},"source":"Crossref","is-referenced-by-count":7,"title":["Reduced expression of SMAD7 and consequent reduction of autophagy promotes endometrial stromal\u2013myofibroblast transition and fibrosis"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6862-6761","authenticated-orcid":false,"given":"Min","family":"Yong","sequence":"first","affiliation":[{"name":"Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Affiliated Hospital of North Sichuan Medical College , Nanchong, Sichuan,","place":["P.R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honggui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Affiliated Hospital of North Sichuan Medical College , Nanchong, Sichuan,","place":["P.R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhua","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Affiliated Hospital of North Sichuan Medical College , Nanchong, Sichuan,","place":["P.R. China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqin","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Affiliated Hospital of North Sichuan Medical College , Nanchong, Sichuan,","place":["P.R. 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