MicroRNA-145 protects follicular granulosa cells against oxidative stress-induced apoptosis by targeting Kruppel-like factor 4
MicroRNA-145 protects follicular granulosa cells against oxidative stress-induced apoptosis by targeting Kruppel-like factor 4
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MicroRNA-145 通过靶向 Kruppel 样因子 4 保护滤泡颗粒细胞免受氧化应激诱导的细胞凋亡
DOI：
10.1016/j.mce.2017.05.030
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发表时间：
2017-09-05
影响因子：
4.1
通讯作者：
Yan, Guijun
中科院分区：
文献类型：
--
作者：
Xu, Lu;Sun, Haixiang;Yan, Guijun
氧化应激诱导的卵泡颗粒细胞（GC）凋亡在异常的卵泡闭锁中起着至关重要的作用，这可能会引发卵巢功能障碍。为了研究microRNA（miR）-145在氧化应激中的GC凋亡调节和凋亡途径的调节中的作用，我们采用了H2O2诱导的体外模型和3硝基离子丙酸（NP）诱导的卵巢氧化应激模型。我们在体外证明了miR-145表达在用H2O2处理的KGN细胞和小鼠颗粒细胞（MGC）中显着下调，而miR-145的过表达减弱了H2O2诱导的GCS中的凋亡。此外，miR-145通过靶向KLF4保护了H2O2诱导的凋亡，从而通过BAX/BCL-2途径促进了H2O2诱导的GC凋亡。重要的是，在体内卵巢氧化应激模型中miR-145的表达降低，通过上调KLF4表达来促进凋亡，而GC特异性miR-145通过靶向KLF4，GC特异性miR-145过表达减弱了细胞凋亡。总之，MiR-145通过靶向KLF4保护GC免受氧化应激诱导的凋亡。 （c）2017年由爱尔兰爱尔兰（Elsevier Ireland Ltd.）出版。
Oxidative stress-induced follicular granulosa cell (GC) apoptosis plays an essential role in abnormal follicular atresia, which may trigger ovarian dysfunction. To investigate the role of microRNA (miR)-145 in the regulation of GC apoptosis and modulation of the apoptotic pathway in the setting of oxidative stress, we employed an H2O2-induced in vitro model and a 3-nitropropionic acid (NP)-induced in vivo model of ovarian oxidative stress. We demonstrated in vitro that miR-145 expression was significantly down-regulated in KGN cells and mouse granulosa cells (mGCs) treated with H2O2, whereas miR-145 over-expression attenuated H2O2-induced apoptosis in GCs. Moreover, miR-145 protected GCs against H2O2-induced apoptosis by targeting KLF4, which promoted H2O2-induced GC apoptosis via the BAX/BCL-2 pathway. Importantly, decreased miR-145 expression in the in vivo ovarian oxidative stress model promoted apoptosis by up-regulating KLF4 expression, whereas GC-specific miR-145 over-expression attenuated apoptosis by targeting KLF4. In conclusion, miR-145 protects GCs against oxidative stress-induced apoptosis by targeting KLF4. (C) 2017 Published by Elsevier Ireland Ltd.