脂肪和肥胖相关基因通过TLR2/p38信号通路促进异位子宫内膜间质细胞纤维化

目的：探讨脂肪和肥胖相关基因（FTO）对异位子宫内膜间质细胞（eESCs）纤维化的影响及其机制。方法：采用实时定量聚合酶链反应（qRT-PCR）检测子宫内膜异位症（EMs）患者病变组织中m6A相关基因的表达；通过慢病毒载体过表达FTO，在eESCs中检测纤维化相关基因的表达；通过m6A2 Target数据库和MeRIP-qPCR预测和验证eESCs中FTO与Toll样受体2（TLR2）的关系；Western blot法检测p38的蛋白表达变化。结果：FTO在EMs中表达下调（P ＜0.05）；FTO过表达促进eESCs纤维化并抑制其增殖（P ＜0.05）；在eESCs中，FTO通过TLR2 的m6A修饰途径上调其蛋白水平（P ＜0.05）；FTO在eESCs中经TLR2/p38 信号通路促进细胞纤维化（P ＜0.05）。结论：FTO在EMs中低表达，上调FTO可能通过TLR2/p38信号通路促进eESCs纤维化。

Fat mass- and obesity-associated gene promotes ectopic endometriotic stromal cells fibrosis via TLR2/p38 axis

Objective: To investigate the effect of FTO on fibrosis of ectopic endometrial mesenchymal cells (eESCs). Methods: m6A-related genes in endometriosis (EMs) were screened and detected, using quantitative real-time polymerase chain reaction (qRT-PCR). Detection of fibrosis-related gene expression in eESCs by overexpression of FTO in a lentiviral vector. Relationship between FTO and TLR2 in eESCs predicted and validated by m6A2 Target site and MeRIP-qPCR. Protein changes in p38 were detected by Western blot. Results:FTO expression was down-regulated in EMs (P<0.05). FTO overexpression promoted fibrosis and inhibited proliferation of eESCs (P<0.05). FTO upregulated its protein level through m6A modification of TLR2 in eESCs (P<0.05). FTO promoted cell fibrosis through TLR2/p38 signaling pathway in eESCs (P<0.05). Conclusion:FTO is low expressed in EMs and upregulation of FTO promotes fibrosis of eESCs through TLR2/p38 signaling pathway.