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

摘要: A range of in vitro, experimental and clinical intervention studies have implicated an important role for hyperglycaemia-induced activation the renin-angiotensin system (RAS) development progression diabetic nephropathy (DN). Blockade RAS by angiotensin converting enzyme (ACE) inhibitors is effective strategy treating kidney diseases. However, few demonstrate mechanism which hyperglycaemia up-regulates expression ACE gene. Our previous identified a novel curcumin analogue, (2E,6E)-2,6-bis(2-(trifluoromethyl)benzylidene)cyclohexanone (C66), could inhibit high glucose (HG)-induced phosphorylation mitogen-activated protein kinases mouse macrophages. In this study, we found that renal protection C66 mice was associated with kinase (MAPK) inactivation ACE/angiotensin II (Ang II) down-regulation. Generally, MAPKs been considered as downstream signalling Ang mediator II-induced pathophysiological actions. using specific small molecule probes, vitro experiments MAPK pathway regulates under HG stimulation, contributes to DN. This study indicates potential candidate DN therapeutic agents, more importantly, reduction inhibition seems be alternative treatment