异位内膜侵袭性生长是子宫内膜异位症（EMs）发生发展的关键。我们前期原创性发现的长链非编码RNA（lncRNA）-TC0101441能促进异位内膜间质细胞（ESCs）迁移侵袭。新近研究发现异位ESCs能分泌富含TC0101441的外泌体，诱导巨噬细胞M2型极化；且TC0101441能结合STAT6促进其磷酸化。据此提出“外泌体传递TC0101441调控STAT6磷酸化修饰，诱导巨噬细胞M2型极化，进而促进EMs侵袭”的假说。本项目拟在分子、细胞、动物、临床层面，探索异位ESCs通过外泌体传递TC0101441诱导巨噬细胞M2型极化的机理及其在EMs侵袭中的作用；探寻TC0101441与STAT6特异性结合的位置及磷酸化位点，解析其调控STAT6磷酸化修饰的机制，以期从“外泌体传递lncRNA”角度揭示EMs侵袭过程中ESCs和巨噬细胞交互对话的新方式，为EMs的复发预测和治疗提供新策略。

The invasive behavior of ectopic endometrium is a critical contributor to endometriosis (EMs) progression.The applicant had ever identified a novel long noncoding RNA (lncRNA)-TC0101441 and found that TC0101441 could promote the migration and invasion of ectopic endometrial stromal cells (ESCs). Further studies found that ectopic ESCs-derived exosomes could carry enriched TC0101441 and modulate the phenotypes of macrophages. Moreover, STAT6 was identified to interact with TC0101441; and TC0101441 could promote STAT6 phosphorylation. Based on these preliminary observations, we propose the following hypothesis: ectopic ESCs can yield exosomes that carry enriched TC0101441.These exosomes can then transfer TC0101441 to recipient macrophages to elicit M2-like polarization through the regulation of STAT6 phosphorylation, eventually facilitating EMs invasion. Accordingly, we plan to explore the mechanistic model explaining how ectopic ESCs prime recipient macrophages toward a M2-like behavior, thereby facilitating EMs invasion. Furthermore, we plan to clarify the underlying molecular mechanism explaining how exosomal TC0101441 interacts with STAT6 and regulats its phosphorylation. These original researches may illustrate a potential cell-cell communication between ESCs and macrophages in an ectopic environment, provide a novel mechanistic model explaining how ectopic ESCs induce EMs invasion from the perspective of the “exosomal transfer of lncRNAs” and highlight the potential clinical value of circulating exosomal TC0101441 in endometriosis.