Send to

Choose Destination
See comment in PubMed Commons below
J Cell Mol Med. 2014 Feb;18(2):231-41. doi: 10.1111/jcmm.12175. Epub 2013 Dec 11.

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

Author information

  • 1Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China; Chinese-American Research Institute for Diabetic Complications, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.


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.


(2E,6E)-2,6-bis(2-(trifluoromethyl)benzylidene)cyclohexanone; angiotensin converting enzyme; diabetic nephropathy; mitogen-activated protein kinases; renin-angiotensin system

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley Icon for PubMed Central
    Loading ...
    Support Center