Inhibition of MAPK-mediated ACE expression by compound C66 prevents STZ-induced diabetic nephropathy

doi:10.1111/jcmm.12175

科研成果详情

题名	Inhibition of MAPK-mediated ACE expression by compound C66 prevents STZ-induced diabetic nephropathy
作者	Pan, Yong 1,2; Huang, Yi 1; Wang, Zhe1; Fang, Qilu 1; Sun, Yusheng3; Tong, Chao 1; Peng, Kesong1; Wang, Yangwei 4; Miao, Lining 4; Cai, Lu2; Zhao, Yunjie1; Liang, Guang1
发表日期	2014-02
发表期刊	JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 影响因子和分区
语种	英语
原始文献类型	Article
关键词	renin-angiotensin system diabetic nephropathy angiotensin converting enzyme mitogen-activated protein kinases (2E 6E)-2 6-bis(2-(trifluoromethyl)benzylidene)cyclohexanone
其他关键词	ANGIOTENSIN-CONVERTING ENZYME ; ACTIVATED PROTEIN-KINASE ; HIGH GLUCOSE ; MESENCHYMAL TRANSITION ; ENDOTHELIAL-CELLS ; RECEPTOR BLOCKADE ; GENE-EXPRESSION ; SYSTEM ; TRANSCRIPTION ; INJURY
摘要	A range of in vitro, experimental and clinical intervention studies have implicated an important role for hyperglycaemia-induced activation of the renin-angiotensin system (RAS) in the development and progression of diabetic nephropathy (DN). Blockade of RAS by angiotensin converting enzyme (ACE) inhibitors is an effective strategy in treating diabetic kidney diseases. However, few studies demonstrate the mechanism by which hyperglycaemia up-regulates the expression of ACE gene. Our previous studies have identified a novel curcumin analogue, (2E,6E)-2,6-bis(2-(trifluoromethyl)benzylidene)cyclohexanone (C66), which could inhibit the high glucose (HG)-induced phosphorylation of mitogen-activated protein kinases in mouse macrophages. In this study, we found that the renal protection of C66 in diabetic mice was associated with mitogen-activated protein kinase (MAPK) inactivation and ACE/angiotensin II (Ang II) down-regulation. Generally, MAPKs have been considered as a downstream signalling of Ang II and a mediator for Ang II-induced pathophysiological actions. However, using C66 and specific inhibitors as small molecule probes, in vitro experiments demonstrate that the MAPK signalling pathway regulates ACE expression under HG stimulation, which contributes to renal Ang II activation and the development of DN. This study indicates that C66 is a potential candidate of DN therapeutic agents, and more importantly, that reduction in ACE expression by MAPKs inhibition seems to be an alternative strategy for the treatment of DN.
资助项目	National 863 key projectNational High Technology Research and Development Program of China [2011AA02A113]; Natural Science Funding of China [81261120560, 21272179, 81300678]; Zhejiang Department of Health; Zhejiang Natural Science Funding [LQ13H310002, Y2110568]; Zhejiang Key Group Project in Scientific Innovation [2010R50042]; Project of Zhejiang Provincial Key Constructive Subject [2012-XK-A28]
出版者	WILEY
出版地	HOBOKEN
ISSN	1582-4934
EISSN	1582-4934
卷号	18 期号:2 页码:231-241
DOI	10.1111/jcmm.12175
页数	11
WOS类目	Cell Biology ; Medicine, Research & Experimental
WOS研究方向	Cell Biology ; Research & Experimental Medicine
WOS记录号	WOS:000330190200005
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	24330074
PMC记录号	PMC3930410
SCOPUSEID	2-s2.0-84893658117
通讯作者地址	[Liang, Guang]Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,China
Scopus学科分类	Molecular Medicine;Cell Biology
引用统计	被引频次：41[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/17102
专题	药学院（分析测试中心）附属第一医院第一临床医学院（信息与工程学院）、附属第一医院_外科学
通讯作者	Liang, Guang
作者单位	1.Chemical Biology Research Center,School of Pharmaceutical Sciences,Wenzhou Medical University,China; 2.Chinese-American Research Institute for Diabetic Complications,School of Pharmaceutical Sciences,Wenzhou Medical University,China; 3.Department of General Surgery,The First Affiliated Hospital of Wenzhou Medical University,China; 4.Department of Nephropathy,The Second Hospital of Jilin University,China
第一作者单位	药学院（分析测试中心）; 生物有机与药物化学研究中心
通讯作者单位	药学院（分析测试中心）; 生物有机与药物化学研究中心
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Pan, Yong,Huang, Yi,Wang, Zhe,et al. Inhibition of MAPK-mediated ACE expression by compound C66 prevents STZ-induced diabetic nephropathy[J]. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,2014,18(2):231-241.
APA	Pan, Yong., Huang, Yi., Wang, Zhe., Fang, Qilu., Sun, Yusheng., ... & Liang, Guang. (2014). Inhibition of MAPK-mediated ACE expression by compound C66 prevents STZ-induced diabetic nephropathy. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 18(2), 231-241.
MLA	Pan, Yong,et al."Inhibition of MAPK-mediated ACE expression by compound C66 prevents STZ-induced diabetic nephropathy".JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 18.2(2014):231-241.