MicroRNA-129-1-3p attenuates autophagy-dependent cell death by targeting MCU in granulosa cells of laying hens under H2O2-induced oxidative stress

文献类型： 外文期刊

第一作者： Zhu, Mingkun

作者： Zhu, Mingkun;Yan, Ming;Chen, Jianfei;Zhang, Yeshun;Zhu, Mingkun;Yan, Ming;Chen, Jianfei;Zhang, Yeshun;Li, Huaiyu

作者机构： Jiangsu Univ Sci & Technol, Sch Biotechnol, Zhenjiang 212100, Peoples R China;Chinese Acad Agr Sci, Sericultural Res Inst, Zhenjiang 212100, Peoples R China;Qingdao Inst Anim Sci & Vet Med, Qingdao Anim Husb Workstat, Qingdao, Shandong, Peoples R China

关键词： microRNA-129-1-3p; MCU; oxidative stress; granulosa cell autophagy; laying hens

期刊名称：POULTRY SCIENCE （ 2022影响因子：4.4； 五年影响因子：4.4 ）

ISSN： 0032-5791

年卷期： 2023 年 102 卷 10 期

页码：

收录情况： SCI

摘要： The present study aimed to investigate the mechanism of microRNA-129-1-3p (miR-129-1-3p) in regulating hydrogen peroxide (H2O2)-induced autophagic death of chicken granulosa cell by targeting mitochondrial calcium uniporter (MCU). The results indicated that the exposure of hens' ovaries to H2O2 resulted in a significant elevation in reactive oxygen species (ROS) levels, as well as the apoptosis of granulosa cells and follicular atresia. This was accompanied by an upregulation of glucose-regulated protein 75 (GRP75), voltage-dependent anion-selective channel 1 (VDAC1), MCU, mitochondria fission factor (MFF), microtubule-associated protein 1 light chain 3 (LC3) I, and LC3II expression, and a downregulation of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1a) and mitofusin-2 (MFN2) expression. In hens' granulosa cells, a luciferase reporter assay confirmed that miR-129-1-3p directly regulates MCU. The induction of oxidative stress through H2O2 resulted in the activation of the permeability transition pore, an overload of calcium, depolarization of the mitochondrial membrane potential, dysfunction of mitochondria-associated endoplasmic reticulum membranes (MAMs), and ultimately, autophagic cell death. The overexpression of miR-129-1-3p effectively mitigated these H2O2-induced changes. Furthermore, miR-129-1-3p overexpression in granulosa cells prevented the alterations induced by H2O2 in the expression of key proteins that play crucial roles in maintaining the integrity of MAMs and regulating autophagy, such as GRP75, VDAC1, MFN2, PTEN-induced kinase 1 (Pink1), and parkin RBR E3 ubiquitin-protein ligase (Parkin). Together, these in vitro-and in vivo-based experiments suggest that miR-129-1-3p protects granulosa cells from oxidative stress-induced autophagic cell death by downregulating the MCU-mediated mitochondrial autophagy. miR-129-1-3p/MCU calcium signaling pathway may act as a new target to alleviate follicular atresia caused by oxidative stress in laying hens.

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