Klotho Protects Against Indoxyl Sulphate-Induced Myocardial Hypertrophy

doi:10.1681/ASN.2014060543

CORC > 北京大学 > 生命科学学院

	Klotho Protects Against Indoxyl Sulphate-Induced Myocardial Hypertrophy
	Yang Ke ; Wang Cheng ; Nie Ling ; Zhao Xiaohui ; Gu Jun ; Guan Xu ; Wang Song ; Xiao Tangli ; Xu Xinli ; He Ting ; Xia Xuefeng ; Wang Junping ; Zhao Jinghong
刊名	journal of the american society of nephrology jasn
	2015
关键词	CKD,left ventricular hypertrophy,uremia
DOI	10.1681/ASN.2014060543
英文摘要	Left ventricular hypertrophy (LVH) is a common complication in patients with CKD and an independent risk factor for death. Changes in the levels of uremic solutes or Klotho have been reported to be related to CKD, whereas the relationships between these factors and CKD-associated LVH remain unclear. Here, we investigated the interaction between Klotho and indoxyl sulfate (IS), a typical uremic solute, in CKD-associated LVH. In a survey of 86 patients with CKD, a negative relationship was found between serum levels of IS and Klotho (r=-0.59, P<0.001). Furthermore, serum levels of IS and Klotho were independently associated with LVH (for IS: r=0.69, P<0.001; for Klotho: r=-0.49, P<0.001). In normal mice, intraperitoneal injection of IS for 8 weeks induced LVH accompanied by substantial downregulation of renal Klotho. Notably, IS-induced LVH was more severe in heterozygous Klotho-deficient (kl/+) mice. In vitro, treatment with Klotho strongly inhibited IS-induced cardiomyocyte hypertrophy by blocking oxidative stress and inhibiting p38 and extracellular signal-regulated protein kinase 1/2 signaling pathways. In a mouse model of CKD-associated LVH, the renal expression of Klotho was lower and the level of serum IS was higher than in healthy controls. Moreover, treatment of CKD mice with Klotho protein significantly restrained the development of LVH. Taken together, these results suggest that Klotho is an endogenous protector against IS-induced LVH, and the imbalance between Klotho and IS may contribute to the development of LVH in CKD.Copyright ? 2015 by the American Society of Nephrology.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000362156700016&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; SCI(E); PubMed; 8; ARTICLE; wangjunping@tmmu.edu.cn; zhaojh@tmmu.edu.cn
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/341372]
专题	生命科学学院
推荐引用方式 GB/T 7714	Yang Ke,Wang Cheng,Nie Ling,et al. Klotho Protects Against Indoxyl Sulphate-Induced Myocardial Hypertrophy[J]. journal of the american society of nephrology jasn,2015.
APA	Yang Ke.,Wang Cheng.,Nie Ling.,Zhao Xiaohui.,Gu Jun.,...&Zhao Jinghong.(2015).Klotho Protects Against Indoxyl Sulphate-Induced Myocardial Hypertrophy.journal of the american society of nephrology jasn.
MLA	Yang Ke,et al."Klotho Protects Against Indoxyl Sulphate-Induced Myocardial Hypertrophy".journal of the american society of nephrology jasn (2015).