Effect of interferon-gamma on transforming growth factor beta/Smad signal pathway and expression of matrix metalloproteinase-2 and tissue inhibitors of matrix metalloproteinase-2 in cultured rat mesangial cells
Xue, A-min.; Wu, H-juan.; Zhang, Z-gang.; Liu, X-guang.; Chen, Q.; Guo, M-yi.
Zhonghua Bing Li Xue Za Zhi 36(6): 405-409
Objective To study the effect of interferon-gamma (IFN-gamma) on the proliferation of mesangial cells (MsC) and transforming growth factor (TGF) -beta/Smad signal pathway, the mRNA and protein expression of matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of matrix metalloproteinase-2 (TIMP-2), and to provide an experimental basis for IFN-gamma treatment of renal fibrosis. Methods Cultured MsC were treated with IFN-gamma at different concentrations and the proliferation of MsC was examined by MTT. Protein and RNA samples were extracted from MsC at 0, 0. 5, 1, 2, 4, 6, 12, 24 h after treated by 100 IU/ ml IFN-gamma. The mRNA and protein expression of Smad3, Smad7, MMP-2 and TIMP-2 were analyzed by realtime RT-PCR and Western blot, respectively. Results The expression of Smad7 mRNA and protein were promptly elevated at 0. 5 hour after the IFN-gamma treatment and lasted for 6 hours, but the proliferation of MsC was not altered. The elevated expression of Smad3, MMP2 mRNA and proteins persisted after 6 hours, whereas the expression of TIMP-2 mRNA and protein decreased. Conclusion The therapeutic effect of IFN-gamma of renal fibrosis may be mediated by TGF-P/smads signal pathway through up-regulation of MMP-2 expression, coupled with down-regulation of TIMP-2 expression.