OTUD1 inhibits endometriosis fibrosis by deubiquitinating MADH7

Xiangyu Chang, Yanqin Zhang, Mengqi Deng, Ruiye Yang, Jiamin Zhang, Menglin Hao, Jinwei Miao
Molecular human reproduction · 2025 · vol. 31(2) · doi:10.1093/molehr/gaaf014 · PMID:40279273 · W4409783565
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OTUD1 deubiquitinates MADH7, inhibiting endometriosis fibrosis progression, lesion growth, and abdominal inflammation in vitro and in vivo.

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Abstract

Fibrosis constitutes the principal pathophysiological mediator of pain and infertility manifestations in endometriosis, and the inhibitory factor of the TGF-β pathway, MADH7, makes a vital impact on the progression of fibrosis. Ovarian tumor domain-containing protein 1 (OTUD1) deubiquitinase binds to the MADH7 protein, although its specific role in endometriosis needs to be investigated. This study is the first to explore the role of OTUD1 in endometriosis and to investigate its impact on the growth of endometriosis lesions in vitro and in vivo, using C57BL/6N female mice and human primary stromal endometriosis cells (HEMCs). Moreover, the obtained results demonstrated that OTUD1 inhibited the expression of fibrosis-related proteins in HEMCs in vitro, and the mechanistic execution of this phenotype was achieved via coordinated deubiquitination coupled with MADH7-mediated transcriptional reprogramming. These events stopped the growth of lesions in vivo and reduced abdominal inflammation. The study demonstrated the critical role of the deubiquitinating enzyme OTUD1 in endometriosis, indicating its potential therapeutic effect on endometriosis.

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Condition tags

mesh:D004715endometriosisinfertility

MeSH descriptors

Deubiquitinating Enzymes Deubiquitinating Enzymes Deubiquitinating Enzymes Deubiquitinating Enzymes Deubiquitinating Enzymes Deubiquitinating Enzymes Deubiquitinating Enzymes Deubiquitinating Enzymes Deubiquitinating Enzymes Deubiquitinating Enzymes Deubiquitinating Enzymes Deubiquitinating Enzymes Deubiquitinating Enzymes Deubiquitinating Enzymes Deubiquitinating Enzymes Deubiquitinating Enzymes Deubiquitinating Enzymes Deubiquitinating Enzymes Deubiquitinating Enzymes Endometriosis

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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