Oxidized LDL stimulates the expression of TGF-β and fibronectin in human glomerular epithelial cells

Guohua Ding, Harry Van Goor, Sharon D. Ricardo, Janis M. Orlowski, Jonathan R. Diamond

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74 Citations (Scopus)

Abstract

Abnormal lipid accumulation in glomeruli is a recognized early event in the development of glomerulosclerosis. The presence of LDL and scavenger receptors has recently been demonstrated in glomerular cells, including the visceral epithelial cells. To explore the possible molecular mechanisms of lipid-induced glomerular injury, the present investigation was conducted to examine the effects of oxidized LDL (ox-LDL) on the expression of transforming growth factor (TGF)-β and fibronectin by cultured human glomerular epithelial cells (GEC). Cultured GEC were exposed to human ox-LDL (0 to 100 μg/ml) for various time points. Ox-LDL induced a dose- and time-dependent increase in the expression of TGF-β mRNA. Actinomycin D, a transcriptional inhibitor, but not cycloheximide, a protein synthesis inhibitor, inhibited the response. GEC exposed to ox-LDL also demonstrated elevated levels of fibronectin mRNA. In addition, treatment of GEC with ox-LDL resulted in increased TGF-β and fibronectin protein expression as detected by immunocytochemistry. Addition of anti-TGF-β antibody significantly inhibited the increase in fibronectin message level induced by ox-LDL. These data suggest that ox-LDL stimulates matrix protein fibronectin in GEC by a mechanism involving expression of TGF-β. Thus, accumulation of lipids in human glomerular epithelial cells may contribute to the pathogenesis of glomerulosclerosis through TGF-β mediated mechanism(s).

Original languageEnglish
Pages (from-to)147-154
Number of pages8
JournalKidney International
Volume51
Issue number1
DOIs
Publication statusPublished - 1 Jan 1997

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