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Exp Biol Med (Maywood). 2011 Apr 1;236(4):435-44. doi: 10.1258/ebm.2010.010325. Epub 2011 Mar 2.

Isoangustone A suppresses mesangial fibrosis and inflammation in human renal mesangial cells.

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1
Department of Food and Nutrition, Hallym University, Chuncheon, Kangwon-do 200-702, South Korea.

Abstract

Development of diabetic nephropathy with fibrosis is associated with hypereglycemia-linked inflammation. Increased levels of proinflammatory factors have been found in diabetic patients with nephropathy. The present study was to test the hypothesis that isoangustone A, a novel compound present in licorice, can inhibit renal fibrosis and inflammation inflamed by high glucose (HG) in human mesangial cells through disturbing transforming growth factor β (TGF-β) and nuclear facor κB (NF-κB) pathways. Serum-starved mesangial cells were cultured in 33 mmol/L glucose media. Cells were treated with 1-20 μmol/L isoangustone A isolated from Glycyrrhiza uralensis licorice for three days. Exposure of cells to HG elevated connective tissue growth factor and collagen production, which was dose-dependently reversed by isoangustone A. Isoangustone A boosted HG-plummeted membrane type matrix metalloproteinase (MMP)-1 expression and diminished HG-elevated tissue inhibitor of MMP-2 expression. HG activated mesangial TGF-β1-SMAD-responsive signaling, which was repealed by ≥10 μmol/L isoangustone A. Furthermore, HG upregulated intracellular cell adhesion molecule-1 (ICAM-1) level and monocyte chemoattractant protein-1 (MCP-1) mRNA expression, and such increases were dose-dependently suppressed by isoangustone A most likely through hampering TGF-β signaling pathways. Blockade of NF-κB signaling appeared to be responsible for attenuating HG-triggered induction of ICAM-1 and MCP-1. Our findings provide the first evidence that isoangustone A dampens mesangial sclerosis associated with inflammation in response to HG through hindering TGF-β and NF-κB signaling.

PMID:
21367880
DOI:
10.1258/ebm.2010.010325
[Indexed for MEDLINE]
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