Experimental study on the effect of tsp-1 on the activation of TGF-β_1 in diabetic nephropathy

Objective To investigate the level of active TGF-β1 in DN rats,and whether inhibiting TSP-1-mediated activation of TGF-β1 could delay the progression of renal fibrosis.Methods Animal model of diabetes was established by intraperitoneal injection of STZ.30 Sprague-Dawley rats were randomized into 3 groups: normal control rats,diabetic rats and diabetic rats treated with polypeptide(100 μg SLKL,daily).Each group consisted of 10 rats.Urinary albumin excretion and serum creatinine were measured every 4 weeks.16 weeks later,kidney pathology was observed.Secreted active and total TGF-β1 in renal tissue supernatant were measured by ELISA.The expression of TGF-β1 and TSP-1 in kidney were observed by immunohistochemistry.Result Urinary albumin excretion,Scr and the pathological changes of kidney in the LSKL-treated group were significantly lower than those in the diabetic rats.The level of total TGF-β1 and active TGF-β1 in renal tissue was higher in diabetic rats and LSKL-treated group than in the normal control group(P0.01).Compared with diabetic rats,the level of active TGF-β1 in LSKL-treated group was significantly lower(P0.01),but the level of total TGF-β1 remained unchanged.In the normal control group,TSP-1 was not detected and there was low expression of TGF-β1.In diabetic rats and LSKL-treated group,there was high expression of TSP-1 and TGF-β1.No significant difference of the expression of TSP-1 and TGF-β1 was observed between diabetic rats and LSKL-treated group(P0.05).Conclusion TSP-1 is the major activator of TGF-β1 in DN rats.Inhibiting TSP-1-mediated activation of TGF-β1 can delay the progression of renal fibrosis.