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  

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

作　　者：王焓 段萍[2] WANG Han;DUAN Ping(Department of Gynecology,the Second Hospital of Harbin Medical University,Harbin 150000,China;Department of Gynecology,the Second Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China)

机构地区：[1]哈尔滨医科大学附属第二医院妇科,黑龙江哈尔滨150000 [2]温州医科大学附属第二医院妇科,浙江温州325000

出　　处：《温州医科大学学报》2022年第3期180-185,193,共7页Journal of Wenzhou Medical University

基　　金：国家自然科学基金项目(82071626,82071619,81671430);浙江省基础公益研究计划项目(LGF21H040010)。

摘　　要：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(q RT-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Me RIP-q PCR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。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.

关 键 词：子宫内膜异位症 m6A修饰 纤维化 TOLL样受体2 P38 

分 类 号：R711[医药卫生—妇产科学]