Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China; Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, 210095, China.
Jiangsu Livestock Embryo Engineering Laboratory, Nanjing Agricultural University, Nanjing, 210095, China.
Theriogenology. 2019 Jul 1;132:72-82. doi: 10.1016/j.theriogenology.2019.04.008. Epub 2019 Apr 11.
Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PPARGC1A) acts as a powerful coactivator of many transcriptional factors that relate to granulosa cell (GC) apoptosis. In this study, the miRNAs mediating goat follicular atresia and luteinized granulosa cell (LGC) apoptosis induced by hydrogen peroxide (HO) via PPARGC1A were investigated. Our results showed that miR-1197-3p targeted PPARGC1A was predicted by bioinformatics algorithm and verified by luciferase reporter assay. In addition, miR-1197-3p promoted goat LGC apoptosis via PPARGC1A through mitochondrial-dependent apoptosis pathway, and these effects could be restored by PPARGC1A overexpression. Moreover, HO-induced LGC apoptosis significantly upregulated miR-1197-3p expression and downregulated PPARGC1A level. Pretreatment of miR-1197-3p inhibitor alleviated LGC apoptosis induced by 400 μM HO for 12 h, and preserved the mitochondrial membrane potential by increasing PPARGC1A expression. In conclusion, miR-1197-3p might act as an essential regulator of goat LGC apoptosis potentially via the mitochondrial-dependent apoptosis pathway by targeting PPARGC1A.
过氧化物酶体增殖物激活受体γ共激活因子 1α（PPARGC1A）作为许多与颗粒细胞（GC）凋亡相关的转录因子的强大共激活因子发挥作用。在这项研究中，研究了通过 PPARGC1A 介导的过氧化氢（HO）诱导的山羊卵泡闭锁和黄体化颗粒细胞（LGC）凋亡的 miRNAs。我们的结果表明，生物信息学算法预测 miR-1197-3p 靶向 PPARGC1A，并通过荧光素酶报告基因检测验证。此外，miR-1197-3p 通过线粒体依赖性凋亡途径通过 PPARGC1A 促进山羊 LGC 凋亡，这些作用可以通过过表达 PPARGC1A 来恢复。此外，HO 诱导的 LGC 凋亡显著上调 miR-1197-3p 的表达并下调 PPARGC1A 水平。miR-1197-3p 抑制剂预处理可减轻 400 μM HO 诱导的 12 h LGC 凋亡，并通过增加 PPARGC1A 表达来维持线粒体膜电位。总之，miR-1197-3p 可能通过靶向 PPARGC1A 作为山羊 LGC 凋亡的重要调节因子通过线粒体依赖性凋亡途径发挥作用。
