宫腔粘连是子宫性不孕的常见原因，纤维化是其特征性病理改变，细胞生物学水平主要体现在内膜间质细胞向肌成纤维细胞转分化。但调控该过程的分子机制不明。我们通过比较纤维化内膜与同期正常内膜表达谱差异发现，环状RNA中的circPTPN12与子宫内膜纤维化相关：该分子仅高表达于纤维化的内膜间质细胞； circPTPN12能与miR-21结合，特异性抑制后者表达。而miR-21能保护子宫内膜避免纤维化，其机制可能是通过靶向SOX9抑制间质细胞向肌成纤维细胞分化。因此我们假说：circPTPN12可抑制miR-21表达使SOX9上调，促进内膜间质细胞向肌成纤维细胞分化，导致子宫内膜纤维化。本课题拟通过临床标本、细胞内分子间调控及动物模型等研究，揭示 circPTPN12-miR-21调控SOX9在维持内膜间质细胞稳态中的机制；提出干预circPTPN12-miR-21-sox9轴抑制内膜纤维化的新策略。

Intrauterine adhesion (IUA) is a common cause of uterine infertility. Fibrosis is the main characteristic pathological change of IUA, which is mainly reflected in the transdifferentiation of endometrial stromal cells into myofibroblasts at the cellular biological level. However, the molecular mechanism regulating this process is unclear. By comparing the expression profiles of fibrotic endometrium with those of normal endometrium in the same menstrual phase, we found that circPTPN12 was associated with endometrial fibrosis: it is only highly expressed in fibrotic endometrial stromal cells. circPTPN12 has several sites to bind miR-21 and specifically inhibit the expression of miR-21. MiR-21 can maintain endometrial structural cell homeostasis so as prevent from fibrosis, which may be through targeting SOX9 to inhibit the differentiation of stromal cells into myofibroblasts. Therefore, we hypothesize that circPTPN12 can inhibit the expression of microRNA-21 and promote the up-regulation of SOX9, thus promoting the differentiation of endometrial stromal cells into myofibroblasts and resulting in endometrial fibrosis. This project aims to reveal the mechanism of circPTPN12-miR-21 regulating SOX9 in maintaining the homeostasis of endometrial stromal cells using clinical specimens, intracellular molecular regulation and animal models to propose a new strategy to interfere with circPTPN12-miR-21-sox9 axis for inhibiting endometrial fibrosis.