Purpose: Renal fibrosis characterized by accumulation of extracellular matrix protein results in chronic renal diseases including diabetic nephropathy. Transforming growth factor β1 (TGF-β1) signaling pathway plays a key role in mediating renal fibrosis. Hence, agents that antagonize TGF-β signaling could be candidate for kidney disease therapy.
Methods: We established renal fibrosis model both in vitro with fibroblast cells treated with rhTGF-β1 and streptozocin(STZ)-induced diabetic nephropathy rats model in vivo and evaluated the effect of the aqueous extract of Lycopus lucidus Turcz, the blood-circulation-promoting Chinese herb, on diabetic nephropathy and investigated the mechanism of action.
Results: We found that Lycopus suppressed rhTGF-β1-induced Smad2 and ERK1/2 activation, down-regulated the expression of TGF-βRI, TGF-βRII, Smad4 and Smad7 in SV40 MES13 cells without inhibiting cell viability. In vivo, lycopus inhibited Smad2 phosphorylation, reduced mRNA level of TGF-β1, ameliorated expansion of the mesangial area in glomerular tissue and reduced the levels of Scr and BUN of serum and total-SOD (superoxide dismutase) activity in STZ-induced diabetic rats.
Conclusion: Lycopus is a novel inhibitor of renal fibrosis by blocking TGF-β signaling pathway and possess a protective effect on renal damage of STZ-induced diabetic nephropathy in rats.
Keywords: Lycopus lucidus; Smad; TGF-β; renal disease.
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