Effects of losartan on expression of matrix metalloproteinase-2,JNK1/2 and proliferation in cardiac fibroblast / 中国临床药理学与治疗学

ABSTRACT

AIM: To elucidate the effects of losartan on the expression ofmatrix 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-freemedia 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 (P＜0.05). 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 (P＜0.05), 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.