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大黄素-8-O-β-D-吡喃葡萄糖苷通过调控长链非编码RNA ANRIL/微小RNA-7a/转化生长因子-β1/信号转导和转录激活因子信号通路抑制高糖诱导的人肾小球系膜细胞凋亡。

Rhein-8-O-β-D-glucopyranoside inhibited high glucose-induced apoptosis of human mesangial cells by regulating the lincRNA ANRIL/let-7a/TGF-β1/Smad signaling pathway.

作者信息

Zhang Lan-Sheng, Li Jing, Jia-Ping Liu

机构信息

School of Pharmacy and Chemistry, Dali University, Dali, Yunnan 671000, P.R. China.

出版信息

Exp Ther Med. 2020 Apr;19(4):2871-2878. doi: 10.3892/etm.2020.8544. Epub 2020 Feb 24.

Abstract

Diabetic nephropathy is one of most frequent complications of diabetes, and is the major cause of end-stage disease in diabetic patients. The present study investigated the roles and mechanisms of Rhein-8-O-β-D-glucopyranoside (Rg) protecting human mesangial cells (HMCs) from high glucose (HG)-induced apoptosis. Using a Cell Counting Kit-8 assay the proliferation of HMCs was analyzed, and flow cytometry was applied to detect apoptosis. The apoptosis-associated protein Bcl-2, caspase-3 and members of the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway were analyzed using a western blotting assay. HG significantly induced HMC apoptosis, and Rg markedly attenuated the HG-induced apoptosis. HG decreased the Bcl-2 expression and increased the caspase-3 expression, and Rg treatment recovered the expressions of Bcl-2 and caspase-3 affected by HG. The underlying mechanisms were further analyzed, and it was demonstrated that HG significantly upregulated the long intervening non-coding RNA (lincRNA) ANRIL expression level, downregulated let-7a expression and activated the TGF-β1/Smad signaling pathway; Rg treatment recovered the expressions of lincRNA ANRIL and let-7a, and inhibited the TGF-β1/Smad signaling pathway in the condition of HG. In conclusion, the present results suggested that Rg attenuated HG-induced apoptosis of HMCs by regulating the lincRNA ANRIL/let-7a/TGF-β1/Smad signaling pathway.

摘要

糖尿病肾病是糖尿病最常见的并发症之一,也是糖尿病患者终末期疾病的主要原因。本研究探讨了大黄酸-8-O-β-D-吡喃葡萄糖苷(Rg)保护人肾小球系膜细胞(HMCs)免受高糖(HG)诱导凋亡的作用及机制。使用细胞计数试剂盒-8法分析HMCs的增殖情况,并采用流式细胞术检测细胞凋亡。采用蛋白质印迹法分析凋亡相关蛋白Bcl-2、caspase-3以及转化生长因子-β1(TGF-β1)/Smad信号通路成员。HG显著诱导HMCs凋亡,而Rg明显减轻了HG诱导的凋亡。HG降低了Bcl-2的表达并增加了caspase-3的表达,Rg处理恢复了受HG影响的Bcl-2和caspase-3的表达。进一步分析其潜在机制,结果表明HG显著上调长链非编码RNA(lincRNA)ANRIL的表达水平,下调let-7a的表达并激活TGF-β1/Smad信号通路;在HG条件下,Rg处理恢复了lincRNA ANRIL和let-7a的表达,并抑制了TGF-β1/Smad信号通路。总之,本研究结果表明Rg通过调节lincRNA ANRIL/let-7a/TGF-β1/Smad信号通路减轻HG诱导的HMCs凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8704/7086228/9e13a7db63e9/etm-19-04-2871-g00.jpg

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