Department of Endocrinology, Yuncheng Central Hospital, Yuncheng, Shanxi 044000, P.R. China.
Henan University School of Basic Medical Sciences, Kaifeng, Henan 475004, P.R. China.
Mol Med Rep. 2017 Oct;16(4):5667-5674. doi: 10.3892/mmr.2017.7224. Epub 2017 Aug 10.
Previous reports have indicated that microRNAs (miRNAs) have an important role in the pathogenesis of diabetic nephropathy (DN). Podocyte apoptosis induced by high glucose (HG) is characteristic of DN. However, the role of miRNAs in HG‑induced podocyte apoptosis remains poorly understood. The present study investigated the role and potential underlying mechanism of miRNA‑20b (miR‑20b) in podocyte apoptosis induced by HG. The results demonstrated that miR‑20b was significantly upregulated in HG‑treated podocytes, as determined by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Caspase‑3 activity and TUNEL assays indicated that suppression of miR‑20b using miR‑20b inhibitors significantly inhibited the podocyte apoptosis induced by HG. Sirtuin 7 (SIRT7) was identified as a functional target of miR‑20b by a Dual‑Luciferase activity reporter assay, RT‑qPCR and western blot analysis. Silencing SIRT7 promoted HG‑induced podocyte apoptosis, as determined by the caspase‑3 activity, while SIRT7 overexpression attenuated HG‑induced podocyte apoptosis. However, SIRT7 silencing significantly blocked the protective effect of miR‑20b suppression against HG‑induced apoptosis. In conclusion, these results indicate that miR‑20b may contribute to HG‑induced podocyte apoptosis by targeting SIRT7, providing a potential therapeutic target for the treatment of DN.
先前的报告表明，微小 RNA（miRNA）在糖尿病肾病（DN）的发病机制中发挥着重要作用。高糖（HG）诱导的足细胞凋亡是 DN 的特征。然而，miRNA 在 HG 诱导的足细胞凋亡中的作用仍知之甚少。本研究探讨了 miRNA-20b（miR-20b）在 HG 诱导的足细胞凋亡中的作用及其潜在机制。结果表明，通过逆转录-定量聚合酶链反应（RT-qPCR）检测到，HG 处理的足细胞中 miR-20b 显著上调。Caspase-3 活性和 TUNEL 检测表明，使用 miR-20b 抑制剂抑制 miR-20b 可显著抑制 HG 诱导的足细胞凋亡。双荧光素酶活性报告基因检测、RT-qPCR 和 Western blot 分析表明，Sirtuin 7（SIRT7）是 miR-20b 的功能靶标。沉默 SIRT7 可促进 HG 诱导的足细胞凋亡，Caspase-3 活性增加，而过表达 SIRT7 可减弱 HG 诱导的足细胞凋亡。然而，SIRT7 沉默显著阻断了 miR-20b 抑制对 HG 诱导的凋亡的保护作用。综上所述，这些结果表明，miR-20b 可能通过靶向 SIRT7 促进 HG 诱导的足细胞凋亡，为 DN 的治疗提供了一个潜在的治疗靶点。
