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A novel compound isoangustone A dampens chronic high glucose‐induced mesangial matrix deposition and fibrosis
Author(s) -
Li Jing,
Lee Eun Sook,
Lim Soon Sung,
Kang YoungHee
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.219.4
Subject(s) - ctgf , glomerulosclerosis , diabetic nephropathy , endocrinology , connective tissue , mesangial cell , medicine , fibrosis , chemistry , smad , secretion , nephropathy , extracellular matrix , growth factor , transforming growth factor , kidney , receptor , diabetes mellitus , biochemistry , proteinuria , pathology
Isoangustone A, a phenolic compound found in licorice, has been shown to exhibit various pharmacological effects including anti‐virus, anti‐allergic and anti‐tumor activities. Glomerulosclerosis is a prominent feature of diabetic nephropathy (DN), which leads to renal failure and end‐stage renal disease. Mesangial matrix mainly comprised of type IV collagen is expanded in DN, where connective tissue growth factor (CTGF) is excessively secreted. The present study was to test whether isoangustone A can inhibit production of collagen and CTGF promoted by high ambient glucose (HG) in human mesangial cells (HRMC). Serum starved HRMC were cultured in media containing 5.5 mM glucose plus 27.5 mM mannitol as an osmotic control or 33 mM glucose for 3 days in the presence of 1–20 μM isoangustone A. Exposure of HRMC to HG caused marked increases in collagen secretion and CTGF expression, which was dose‐dependently suppressed by isoangustone A. Furthermore, isoangustone A appeared to retard HG‐triggered matrix expansion, repealing MT1‐MMP attenuation and TIMP‐2 elevation accompanied by HG. Such effects of isoangustone A was mediated most likely through disturbing TGF‐β/Smad signaling pathways. The results demonstrate that isoangustone A may be a potential therapeutic agent for the prevention and treatment of glomerulosclerosis.