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miR-21 通过靶向 PDCD4 减轻对比剂诱导的肾小管细胞凋亡。

miR‑21 attenuates contrast‑induced renal cell apoptosis by targeting PDCD4.

机构信息

Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Key Laboratory of Coronary Disease, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510515, P.R. China.

出版信息

Mol Med Rep. 2017 Nov;16(5):6757-6763. doi: 10.3892/mmr.2017.7426. Epub 2017 Sep 5.

Abstract

Contrast medium (CM) is widely used in cardiac catheterization; however, it may induce acute kidney injury or renal failure, although the underlying mechanism remains to be elucidated. MicroRNA‑21 (miR‑21) is involved in renal disease and has been indicated to regulate cellular apoptosis and fibrosis, although its role in CM‑induced renal cell injury is unknown. The present study examined the expression and potential targets of miR‑21 in human renal proximal tubular epithelial (HK‑2) cells following CM treatment. CM induced renal cell apoptosis and decreased miR‑21 expression. The expression level of the apoptosis regulator protein, B‑cell lymphoma 2 (Bcl‑2) was upregulated, whereas that of the apoptosis regulator, Bcl‑2‑associated X protein (Bax) was downregulated upon transfection of miR‑21 mimics; miR‑21 overexpression additionally directly inhibited the expression of programmed cell death protein 4 (PDCD4), as determined by a dual luciferase reporter assay, and PDCD4 silencing reduced the rate of HK‑2 cell apoptosis. The results of the present study indicated that miR‑21 protected renal cells against CM‑induced apoptosis by regulating PDCD4 expression.

摘要

对比剂(CM)广泛应用于心导管检查;然而,它可能会引起急性肾损伤或肾衰竭,尽管其潜在机制仍有待阐明。微小 RNA-21(miR-21)参与肾脏疾病,并且已经表明其可调节细胞凋亡和纤维化,尽管其在 CM 诱导的肾细胞损伤中的作用尚不清楚。本研究检测了 CM 处理后人类肾近端管状上皮(HK-2)细胞中 miR-21 的表达及其潜在靶标。CM 诱导肾细胞凋亡并降低 miR-21 的表达。转染 miR-21 模拟物后,凋亡调节剂蛋白 B 细胞淋巴瘤 2(Bcl-2)的表达上调,而凋亡调节剂 Bcl-2 相关 X 蛋白(Bax)的表达下调;双荧光素酶报告基因检测表明,miR-21 过表达还直接抑制程序性细胞死亡蛋白 4(PDCD4)的表达,并且 PDCD4 沉默减少 HK-2 细胞的凋亡率。本研究的结果表明,miR-21 通过调节 PDCD4 的表达来保护肾细胞免受 CM 诱导的凋亡。

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