Effects of all-trans retinoic acid on the expression of bone morphogenetic protein-7 and the metabolism of extracellular matrix in kidney tissues of streptozotocin-induced diabetic rats

AIM To explore the effects of all-trans retinoic acid(atRA) on the expression of bone morphogenetic protein-7(BMP-7),transforming growth factor-β1(TGF-β1) and the metabolism of collagen Ⅳ,collagen Ⅲ in kidney tissues of streptozotocin(STZ)-induced diabetic rats.METHODS Rats injected with STZ were randomly divided into model group(DM)and therapy group(DM+atRA).Other 12 normal rats were used as control group(NC).The treatment was lasted for 8 weeks or 12 weeks,and renal pathological change was evaluated by light and electron microscopy.The expression of BMP-7,TGF-β1 and collagen Ⅳ,collagen Ⅲ in kidney tissues were tested by immunohistochemistry technique.The mRNA expression of BMP-7 and TGF-β1 in kidney tissues was quantitatively determined through real time reverse transcription polymerase chain reaction(real time RT-PCR).RESULTS The expression of BMP-7 in kidney in DM+atRA group was significantly higher than that in DM group(P0.01),but the expression of TGF-β1,collagen Ⅲ and Ⅳ of kidney in DM+atRA group was significantly lower than that in DM group(P0.01).And the levels of protein exprssion of BMP-7 were negatively correlated with the levels of TGF-β1(r=-0.86,P0.01),collagen Ⅳ(r=-0.75,P0.01)and collagen Ⅲ(r=-0.71,P0.01),respectively.The levels of mRNA exprssion of BMP-7 in kidney in DM+atRA group were higher than those in DM group(P0.01),but the levels of TGF-β1 lower than those in DM group(P0.01).Also the levels of mRNA exprssion of BMP-7 were negatively correlated with the levels of TGF-β1(r=-0.83,P0.01).CONCLUSION The atRA can relieve renal injury and inhibit renal fibrosis in rats with diabetic nephropathy induced by STZ,which might be related to the up-regulating of the expression of BMP-7 and the down-regulating the expression of TGF-β1 expression in kidney tissues.