OTUD1 inhibits endometriosis fibrosis by deubiquitinating MADH7

Xiangyu Chang1, Yanqin Zhang1, Mengqi Deng1

  • 1Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing, China.

PubMed

Insights

Ovarian tumor domain-containing protein 1 (OTUD1) inhibits endometriosis fibrosis by deubiquitinating MADH7. This finding reveals OTUD1 as a potential therapeutic target for reducing endometriosis-related pain and infertility.

Area of Science:

  • Reproductive biology
  • Molecular oncology
  • Cellular biology

Background:

  • Fibrosis is a key factor in endometriosis-associated pain and infertility.
  • MADH7, a TGF-β pathway inhibitor, influences fibrosis progression.
  • The role of Ovarian tumor domain-containing protein 1 (OTUD1) in endometriosis is not well understood.

Purpose of the Study:

  • To investigate the role of OTUD1 in endometriosis.
  • To determine OTUD1's impact on endometriosis lesion growth in vitro and in vivo.

Main Methods:

  • Utilized C57BL/6N female mice and human primary endometrial stromal cells (HEMCs).
  • Assessed OTUD1's effect on fibrosis-related protein expression in HEMCs.
  • Investigated the mechanism involving deubiquitination and MADH7-mediated transcriptional reprogramming.

Main Results:

  • OTUD1 inhibited fibrosis-related protein expression in HEMCs.
  • OTUD1 deubiquitination of MADH7 reprogrammed transcription, halting lesion growth in vivo.
  • Reduced abdominal inflammation was observed in vivo.

Conclusions:

  • OTUD1 plays a critical role in regulating fibrosis in endometriosis.
  • OTUD1's mechanism involves MADH7-mediated transcriptional reprogramming.
  • OTUD1 demonstrates potential as a therapeutic agent for endometriosis.