MicroRNA-145 protects follicular granulosa cells against oxidative stress-induced apoptosis by targeting Krüppel-like factor 4

Publication date: Available online 28 May 2017
Source:Molecular and Cellular Endocrinology
Author(s): Lu Xu, Haixiang Sun, Mei Zhang, Yue Jiang, Chunxue Zhang, Jianjun Zhou, Lijun Ding, Yali Hu, Guijun Yan
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.



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