[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]

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 real-time 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-beta/smads signal pathway through up-regulation of MMP-2 expression, coupled with down-regulation of TIMP-2 expression.