过氧化物酶体增殖物激活受体γ（PPARγ）通过调节MAT2A基因的转录来诱导子宫内膜异位症的发作。
PPARγ induces the paroxysm of endometriosis by regulating the transcription of MAT2A gene.
作者信息
Zhang Shun, Zhuang Lingling, Liu Qian, Yu Xiaolin, Min Qinghua, Chen Minjie, Chen Qi
机构信息
The First Affiliated Hospital of Nanchang University No. 17 Yongwaizheng Street, Donghu District, Nanchang, Jiangxi, People's Republic of China.
出版信息
Am J Transl Res. 2021 Mar 15;13(3):1377-1388. eCollection 2021.
OBJECTIVE
To investigate the molecular mechanism of PPARγ impacting the paroxysm of endometriosis.
METHODS
Immunohistochemistry, qRT-PCR and Western Blot were used to determine the expression level of PPARγ and MAT2A in Eu, Ec and normal endometrial tissue (control). ESC and NSC were separately isolated. PPARγ was silenced in NSC and was up-regulated in ESC. Rosiglitazone (RSG) were used to incubate with ESC. Proliferation, apoptosis, invasion, and ultrastructure of cells were evaluated in vitro. The combination between PPARγ and the promoters of MAT2A was detected by dual-luciferase reporter assay.
RESULTS
MAT2A was up-regulated and PPARγ was down-regulated in Eu and Ec. The cell viability and the ability of migration and invasion declined greatly after up-regulating the expression of PPARγ or treating with RSG in ESC. Meanwhile, the expression level of MAT2A was significantly inhibited. Plenty of vacuoles and classical morphological changes of apoptotic cells were observed in the ESC with PPARγ over-expressed. The cell viability and the ability of migration and invasion of NSC with PPARγ silenced were promoted greatly. Meanwhile, the expression level of MAT2A was significantly up-regulated.
CONCLUSION
The paroxysm and development of endometriosis were impacted by over-expressing PPARγ or introducing of RSG by inhibiting the transcription of MAT2A.
目的
探讨过氧化物酶体增殖物激活受体γ（PPARγ）影响子宫内膜异位症发病的分子机制。
方法
采用免疫组织化学、实时定量聚合酶链反应（qRT-PCR）和蛋白质免疫印迹法检测PPARγ和蛋氨酸腺苷转移酶2A（MAT2A）在在位内膜（Eu）、异位内膜（Ec）及正常子宫内膜组织（对照）中的表达水平。分别分离子宫内膜间质细胞（ESC）和正常子宫内膜间质细胞（NSC）。在NSC中沉默PPARγ，在ESC中上调PPARγ。用罗格列酮（RSG）处理ESC。体外评估细胞的增殖、凋亡、侵袭及超微结构。通过双荧光素酶报告基因检测法检测PPARγ与MAT2A启动子之间的结合情况。
结果
Eu和Ec中MAT2A表达上调，PPARγ表达下调。在ESC中上调PPARγ表达或用RSG处理后，细胞活力以及迁移和侵袭能力显著下降。同时，MAT2A的表达水平受到明显抑制。在PPARγ过表达的ESC中观察到大量空泡及凋亡细胞的典型形态学变化。PPARγ沉默的NSC的细胞活力以及迁移和侵袭能力显著增强。同时，MAT2A的表达水平明显上调。
结论
过表达PPARγ或引入RSG通过抑制MAT2A的转录影响子宫内膜异位症的发病及发展。
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