Emodin suppresses hyperglycemia-induced proliferation and fibronectin expression in mesangial cells via inhibiting cFLIP.

Abstract

As one of the most serious microvascular complications of diabetes and a major cause of end stage renal disease, diabetic nephropathy (DN) is calling for effective treatment strategies. Here, we provide evidence that hyperglycemia can induce proliferation and decreasing apoptosis of mesangial cells (MCs) and subsequent renal dysfunction by up-regulating cellular FLICE-inhibitory protein (cFLIP). Treatment with emodin significantly turns down the accelerated cell cycle and proliferation of MCs cultured in high glucose (HG) via inhibiting cFLIP. In vitro, knockdown of cFLIP can arrest cell cycle and accelerate cell death by activating caspase-8, caspase-3 and caspase-9, and down-regulate proliferating cell nuclear antigen (PCNA). Our results also suggest that emodin regulates cFLIP expression in transcriptional level. Importantly, emodin lessens proteinuria and fibronectin expression in early-stage of streptozotocin (STZ)-induced diabetic rats. These findings demonstrate that emodin represent a promising strategy to prevent renal dysfunction in early-stage of diabetes mellitus.