子宫内膜异位症的新机制：缺氧ESCs外泌体来源的LncRNA RAD51-AS1通过FTO调控JAK2 m6A去甲基化促进巨噬细胞M2型极化

M2型巨噬细胞在子宫内膜异位症（EMs）发生发展中起着重要作用，可促进异位内膜间质细胞（ESCs）增殖、侵袭及血管生成，使异位内膜发生免疫逃逸，但巨噬细胞M2型极化机制仍有待阐明。我们前期发现：在缺氧ESCs外泌体中LncRNA RAD51-AS1显著高表达，且能促进巨噬细胞M2型极化；RAD51-AS1能调控巨噬细胞中FTO的表达。因此，我们假设：缺氧ESCs外泌体来源的RAD51-AS1通过FTO调控JAK2/STAT3信号通路分子m6A的去甲基化，促进巨噬细胞M2型极化。本项目拟通过ChIRP、MeRIP-seq等技术证明RAD51-AS1、FTO启动子和转录因子形成三元复合体调控FTO转录，进而引起JAK2等下游分子m6A的去甲基化，促进巨噬细胞M2型极化，参与EMs病灶形成。本项目旨在深入解析缺氧状态下ESCs和巨噬细胞之间的生物信号传递体系，以期为EMs干预提供新的思路和靶点。

M2 macrophages play an important role in the development of endometriosis (EMs). They can promote the proliferation, invasion and angiogenesis of ESCs, and make the immune escape of endometrium. However, alternatively activated mechanism of macrophages remains to be elucidated. We previously found that the expression of LncRNA RAD51-AS1 was significantly high in the exosomes of hypoxic ESCs, and it could promote alternatively activation of macrophages. RAD51-AS1 could regulate the expression of FTO in macrophages. Therefore, we hypothesized that RAD51-AS1 derived from hypoxic ESCs exosomes could promote alternatively activation of macrophages by regulating the demethylation of JAK2/STAT3 signaling pathway molecule m6A through FTO. In this project, ChIRP and MeRIP-seq are used to prove that RAD51-AS1, FTO promoter and transcription factor form a ternary complex to regulate FTO transcription, so as to cause demethylation of downstream molecule m6A such as JAK2, which promotes alternatively activation of macrophages and participates in the formation of EMs lesions. The purpose of this project is to deeply elucidate the biological signaling system between hypoxic ESCs and macrophages, in order to provide new ideas and targets for EMs intervention.