Effects Of Fluvastatin On The Cellular Proliferation And The Expression Of Connective Tissue Growth Factor And Type Ⅳ Collagen In Mesangial Cells

Objective: To investigate the effects of fluvastatin(Flu) on the cellular proliferation and the expression of connective tissue growth factor (CTGF) and typeⅣcollagen (ColⅣ) in rat mesangial cells (MCs) induced by transforming growth factor-β1(TGF-β1),and to explore the possible mechanisms of Flu for renoprotection.Methods: MCs were divided into the following groups according to different factors: Control group, TGF-β1(different time and concentration) group, TGF-β1 + Fluvastatin (different concentration) group. The cellular proliferation was detected by MTT, the expression of CTGF was measured using RT-PCR and Western Blot respectively and the secretion of ColⅣprotein was quantitated by ELISA. Simultaneously MCs were stimulated by exogenous CTGF (different concentration) and the secretion of ColⅣwas detected by ELISA.Results: (1) TGF-β1 promoted the proliferation of MCs in a dose-dependent manner and the promotion of 5ng/ml TGF-β1 was maximal. The proliferation of MCs decreased as the concertration of TGF-β1 increased when TGF-β1 exceeded 10ng/ml. 30 ng/ml TGF-β1 could hardly promote the celluar proliferation compared with the control group. Flu could inhibit the proliferation of MCs induced by 5ng/ml TGF-β1 in a dose-dependent manner: 1μmol/L Flu could just suppress the proliferation significantly,P<0.01. (2)The expression of CTGFmRNA and protein were upregulated by 10ng/ml TGF-β1 in a time-dependent manner. The promotion of TGF-β1 was maximal at 9h and 12h respectively. The expression of CTGFmRNA and protein were upregulated by TGF-β1 in a dose-dependent manner and the promotion of 10ng/ml TGF-β1 was maximal. Flu could inhibit the expression of CTGFmRNA and protein induced by 5ng/ml TGF-β1 in a dose-dependent manner: 1μmol/L Flu could just suppress the expression of mRNA significantly,P<0.01; 10μmol/L Flu could just suppress the expression of protein significantly,P<0.01.(3)5ng/ml TGF-β1 could upregulate the expression of ColⅣin MCs significantly,P<0.01. Flu could inhibit the expression of ColⅣin MCs induced by 5ng/ml TGF-β1 in a dose-dependent manner: 0.1μmol/L Flu could just suppress the expression of ColⅣsignificantly, P<0.01.(4)Exogenous CTGF could promote the expression of ColⅣin a dose-dependent manner. 2.5ng/ml CTGF could just promote the expression of ColⅣsignificantly, P<0.05.Conclusions: (1) TGF-β1 can promote the celluar proliferation and the expression of CTGF and ColⅣin MCs in a time- and dose-dependent manner.(2)Fluvastatin can inhibit the celluar proliferation and the high expression of CTGF and ColⅣinduced by TGF-β1 in a dose-dependent manner.(3)Fluvastatin can suppress the expression of ColⅣinduced by TGF-β1 in a dose-dependent manner.This inhibitory effect may be attributed to suppressing the expression of CTGF.