OTUD1 inhibits endometriosis fibrosis by deubiquitinating MADH7

Abstract Fibrosis constitutes the principal pathophysiological mediator of pain and infertility manifestations in endometriosis, and the inhibitory factor of TGF-β pathway, MADH7, makes a vital impact on the progression of fibrosis. Ovarian tumour domain-containing protein 1 (OTUD1) deubiquitinase binds to the MADH7 protein, although its specific role in endometriosis needs to be explored. 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 primary human 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.