MicroRNA-122-5p alleviates endometrial fibrosis via inhibiting the TGF-β/SMAD pathway in Asherman's syndrome

Abstract

Research question: What is the effect of miR-122 on the progression and recovery of fibrosis in Asherman's syndrome?

Design: Endometrial tissue was collected from 21 patients, 11 with intrauterine adhesion (IUA) and 10 without IUA. Quantitative real-time polymerase chain reaction, immunofluorescence and Western blot were applied to observe the expression of mRNAs/miRNAs and protein, respectively. The endometrial physical injury was carried out in C57BL/6 mice to create an endometrial fibrosis model, with intrauterine injection of adenovirus to compare the antifibrosis and repair function of miR-122 on endometrium. The morphology of the uterus was observed using haematoxylin and eosin staining, and fibrosis markers were detected by immunohistochemistry.

Results: miR-122 expression was reduced in patients with IUAs, accompanied by fibrosis. MiR-122 overexpression reduced the degree of fibrosis in endometrial stromal cells. Further molecular analyses demonstrated that miR-122 inhibited fibrosis through the TGF-β/SMAD pathway by directly targeting the 3' untranslated region of SMAD family member 3, suppressing its expression. Notably, miR-122 promoted endometrial regeneration and recovery of pregnancy capacity in a mouse endometrial injury model.

Conclusions: miR-122 is a critical regulator for repair of endometrial fibrosis and provided new insight for the clinical treatment of intrauterine adhesions.

Keywords: SMAD transcription factor; fibrosis; intrauterine adhesion; microRNA (miRNA); reproduction; transforming growth factor beta (TGF‐β).