MicroRNA-30e targets BNIP3L to protect against aldosterone-induced podocyte apoptosis and mitochondrial dysfunction
MicroRNA-30e targets BNIP3L to protect against aldosterone-induced podocyte apoptosis and mitochondrial dysfunction
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DOI：
10.1152/ajprenal.00486.2016
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发表时间：
2017-04-01
影响因子：
4.2
通讯作者：
Zhang, Aihua
中科院分区：
文献类型：
--
作者：
Guo, Yan;Deng, Xu;Zhang, Aihua
microRNA对于维持足细胞稳态是必不可少的。新出现的证据已经证明了microRNA-30 a（miR-30 a）（miR-30家族的成员）在足细胞损伤中的保护作用。然而，其他miR-30家族成员在足细胞损伤中的作用尚不清楚。本研究旨在探讨miR-30 e在醛固酮（aldosterone，Aldo）诱导足细胞损伤中的作用及其机制。Aldo处理后，miR-30 e以剂量和时间依赖性方式减少。值得注意的是，miR-30 e的过表达显著减弱了足细胞中Aldo诱导的凋亡。与这一发现一致，miR-30 e沉默导致显著的足细胞凋亡。线粒体功能障碍（MtD）已被证明是醛诱导的足细胞损伤的早期事件。我们发现miR-30 e的过表达改善了Aldo诱导的MtD，而miR-30 e的沉默导致了MtD。接下来，我们发现miR-30 e可以直接靶向BCL 2/腺病毒E1 B相互作用蛋白3样（BNIP 3L）基因。Aldo显著增强足细胞中BNIP 3L的表达，并且BNIP 3L的沉默在很大程度上消除了Aldo诱导的MtD和细胞凋亡。相反，BNIP 3L的过表达诱导足细胞的MtD和凋亡。总之，这些发现表明miR-30 e通过靶向BNIP 3L保护线粒体和足细胞免受Aldo攻击。
MicroRNAs are essential for the maintenance of podocyte homeostasis. Emerging evidence has demonstrated a protective role of microRNA-30a (miR-30a), a member of the miR-30 family, in podocyte injury. However, the roles of other miR-30 family members in podocyte injury are unclear. The present study was undertaken to investigate the contribution of miR-30e to the pathogenesis of podocyte injury induced by aldosterone (Aldo), as well as the underlying mechanism. After Aldo treatment, miR-30e was reduced in a dose-and time-dependent manner. Notably, overexpression of miR-30e markedly attenuated Aldo-induced apoptosis in podocytes. In agreement with this finding, miR-30e silencing led to significant podocyte apoptosis. Mitochondrial dysfunction (MtD) has been shown to be an early event in Aldo-induced podocyte injury. Here we found that overexpression of miR-30e improved Aldo-induced MtD while miR-30e silencing resulted in MtD. Next, we found that miR-30e could directly target the BCL2/adenovirus E1B-interacting protein 3-like (BNIP3L) gene. Aldo markedly enhanced BNIP3L expression in podocytes, and silencing of BNIP3L largely abolished Aldo-induced MtD and cell apoptosis. On the contrary, overexpression of BNIP3L induced MtD and apoptosis in podocytes. Together, these findings demonstrate that miR-30e protects mitochondria and podocytes from Aldo challenge by targeting BNIP3L.