Abstract
Resveratrol (Resv) is natural polyphenol found in grapes. This study evaluated the protective effect of Resv against the effects of uric acid (UA) in immortalized human mesangial cells (ihMCs). ihMCs were preincubated with Resv (12.5 µM) for 1 h and treated with UA (10 mg/dL) for 6 or 12 h. The intracellular calcium concentration [Ca2+]i was quantified by fluorescence using flow cytometry. Angiotensinogen (AGT) and pre-pro endothelin-1 (ppET-1) mRNA were assayed by quantitative real-time RT-PCR. Angiotensin II (AII) and endothelin-1 (ET-1) were assayed by ELISA. UA significantly increased [Ca2+]i. Pre-incubation with Resv significantly reduced the change in [Ca2+]i induced by UA. Incubation with UA for 6 or 12 h also increased AGT mRNA expression and AII protein synthesis. Resv blunted these increases in AGT mRNA expression and AII protein. Incubation with UA in the ihMCs increased ppET-1 expression and ET-1 protein synthesis at 6 and 12 h. When ihMCs were pre-incubated with Resv, UA had a significantly diminished effect on ppET-1 mRNA expression and ET-1 protein synthesis at 6 and 12 h, respectively. Our results suggested that UA triggers reactions including AII and ET-1 production in mesangial cells. The renin-angiotensin system may contribute to the pathogenesis of renal function and chronic kidney disease. Resv can minimize the impact of UA on AII, ET-1 and the increase of [Ca2+]i in mesangial cells, suggesting that, at least in part, Resv can prevent the effects of soluble UA in mesangial cells.
Highlights
Resveratrol (Resv), a phenolic compound with significant biological activity, is of great interest to several research groups worldwide [1,2]
This study evaluated the protective effect of Resv against the effects of uric acid (UA) in immortalized human mesangial cells. ihMCs were preincubated with Resv (12.5 mM) for 1 h and treated with UA (10 mg/dL) for 6 or 12 h
Our results suggested that UA triggers reactions including Angiotensin II (AII) and ET-1 production in mesangial cells
Summary
Resveratrol (Resv), a phenolic compound with significant biological activity, is of great interest to several research groups worldwide [1,2]. Dietary intake of Resv in grapes, red wine, peanuts, purple grape juice, and berries may have beneficial effects on human heath [1,2,3,4,5,6,7], and may have health-promoting antinephrolithic, antidiabetes, anticancer, antioxidation, anti-inflammation, cardioprotective, chemopreventive, and neuroprotective properties [5,6,7,8,9]. Resv may prevent renal lipotoxicity and have antihyperuricemic activity [10,11]. Resv exerts its antinephrolithic potential via the inhibition of ROS, monocyte chemoattractant protein-1 (MCP-1), hyaluronan, and osteopontin (OPN) signaling [13]. Resv has been shown to suppress the migration of oxalate-treated human renal epithelial cells (HRCs), It can attenuate the expression of NADPH oxidase subunit, MCP-1, and OPN mRNAs, and downregulate the expression of transforming growth factor-b (TGF-b1), TGF-b receptor and hyaluronan proteins in oxalate-treated HRCs [13]
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