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.
- Author:
Ai-min XUE
1
;
Hui-juan WU
;
Zhi-gang ZHANG
;
Xue-guang LIU
;
Qi CHEN
;
Mu-yi GUO
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Cell Proliferation; drug effects; Cells, Cultured; Interferon-gamma; pharmacology; Matrix Metalloproteinase 2; genetics; metabolism; Mesangial Cells; cytology; metabolism; RNA, Messenger; metabolism; Rats; Recombinant Proteins; Signal Transduction; Smad3 Protein; genetics; metabolism; Smad7 Protein; genetics; metabolism; Tissue Inhibitor of Metalloproteinase-2; genetics; metabolism; Transforming Growth Factor beta; metabolism
- From: Chinese Journal of Pathology 2007;36(6):405-409
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo 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.
METHODSCultured 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.
RESULTSThe 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.
CONCLUSIONThe 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.