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肾脏保护:聚焦于瞬时受体电位香草酸亚型1、瞬时受体电位香草酸亚型4、瞬时受体电位阳离子通道亚家族C成员6和瞬时受体电位 melastatin 2

Renoprotection: focus on TRPV1, TRPV4, TRPC6 and TRPM2.

作者信息

Markó L, Mannaa M, Haschler T N, Krämer S, Gollasch M

机构信息

Experimental and Clinical Research Center, A Joint Cooperation Between the Charité Medical Faculty and the Max-Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany.

Charité Campus Virchow, Nephrology/Intensive Care, Berlin, Germany.

出版信息

Acta Physiol (Oxf). 2017 Mar;219(3):589-612. doi: 10.1111/apha.12828. Epub 2016 Dec 28.

Abstract

Members of the transient receptor potential (TRP) cation channel receptor family have unique sites of regulatory function in the kidney which enables them to promote regional vasodilatation and controlled Ca influx into podocytes and tubular cells. Activated TRP vanilloid 1 receptor channels (TRPV1) have been found to elicit renoprotection in rodent models of acute kidney injury following ischaemia/reperfusion. Transient receptor potential cation channel, subfamily C, member 6 (TRPC6) in podocytes is involved in chronic proteinuric kidney disease, particularly in focal segmental glomerulosclerosis (FSGS). TRP vanilloid 4 receptor channels (TRPV4) are highly expressed in the kidney, where they induce Ca influx into endothelial and tubular cells. TRP melastatin (TRPM2) non-selective cation channels are expressed in the cytoplasm and intracellular organelles, where their inhibition ameliorates ischaemic renal pathology. Although some of their basic properties have been recently identified, the renovascular role of TRPV1, TRPV4, TRPC6 and TRPM2 channels in disease states such as obesity, hypertension and diabetes is largely unknown. In this review, we discuss recent evidence for TRPV1, TRPV4, TRPC6 and TRPM2 serving as potential targets for acute and chronic renoprotection in chronic vascular and metabolic disease.

摘要

瞬时受体电位(TRP)阳离子通道受体家族成员在肾脏中具有独特的调节功能位点,这使它们能够促进局部血管舒张,并控制钙离子流入足细胞和肾小管细胞。已发现激活的TRP香草酸受体1通道(TRPV1)在缺血/再灌注后急性肾损伤的啮齿动物模型中引发肾脏保护作用。足细胞中的瞬时受体电位阳离子通道亚家族C成员6(TRPC6)参与慢性蛋白尿性肾病,尤其是局灶节段性肾小球硬化(FSGS)。TRP香草酸受体4通道(TRPV4)在肾脏中高度表达,可诱导钙离子流入内皮细胞和肾小管细胞。TRP褪黑素(TRPM2)非选择性阳离子通道在细胞质和细胞内细胞器中表达,抑制它们可改善缺血性肾脏病理。尽管最近已确定了它们的一些基本特性,但TRPV1、TRPV4、TRPC6和TRPM2通道在肥胖、高血压和糖尿病等疾病状态下的肾血管作用在很大程度上仍不清楚。在本综述中,我们讨论了TRPV1、TRPV4、TRPC6和TRPM2作为慢性血管和代谢疾病中急性和慢性肾脏保护潜在靶点的最新证据。

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