Effects of losartan on expression of matrix metalloproteinase-2,JNK1/2 and proliferation in cardiac fibroblast

AIM: To elucidate the effects of losartan on the expression of matrix metalloproteinases-2,JNK1/2 and proliferation in cardiac fibroblast.METHODS: Neonatal rat cardiac fibroblasts were cultured.The cells proliferation was determined by MTT.To determine effects of AngⅡ on JNK1/2 activity,cells were incubated(for 0,2,5,10,30,60,120 min) in serum-free media with AngⅡ,and the other group fibroblasts were exposed to serum-free media with or without AngⅡ and losartan(AngⅡ 100 nmol/L,AngⅡ 100 nmol/L+losartan 100 nmol/L,losartan100 nmol/L,losartan for 45 min before).Cells protein was collected with MBST buffer.The relative abundance of MMP-2,JNK1/2 and p-JNK1/2 in cells was determined by immunoblotting.The secretion of MMP-2 in media of cell culture was determined by ELISA.RESULTS: AngⅡ increased the proliferation of CFB in a dose-dependent manner,whereas losartan decreased the proliferation of CFB stimulated by AngⅡ in a dose-dependant manner,too(P0.05).The relative abundance of JNK1/2 was highest in AngⅡ of the 2-min-stimulated group.AngⅡincreased expression of JNK1/2 and MMP-2 protein(P0.05),on the contrary,losartan inhibited JNK1/2 and MMP-2 protein expression. CONCLUSION: AngⅡ induce the increase of proliferation of CFB,expression of JNK1/2 and MMP-2 in CFB,and losartan inhibits these effects of AngⅡ.