Effects of mycophenolate mofetil on transdifferentiation and function of lung fibroblasts / 中国免疫学杂志

ABSTRACT

Objective:To investigate the effects of mycophenolate mofetil ( MMF) on the differentiation and connective tissue growth factor(CTGF)and fibronectin(FN)expression of lung fibroblasts(LF)through interfering the transdifferentiation of LF into MF in vitro.Methods:LF of neonatal rat were cultured in vitro ,induced into MF by transforming growth factor-β1(TGF-β1),and treated with different concentrations of MMF ,which was 0μmol/L(control group),0.1μmol/L(low dose group),1μmol/L(middle dose group)or 10 μmol/L( high dose group ) .Morphology of LF and MF were observed by inverted phase contrast microscope , the expressions of vimentin and α-smooth muscle actin (α-SMA) were identified by immunofluorescence staining ,and then analyzed the effect of MMF on the transdifferentiation of fibroblasts .ELISA was used to detect the levels of connective tissue growth factor ( CTGF ) and fibronectin ( FN) .Results: LF was induced into MF by TGF-β196 hours later.The immune fluorescence performance of α-SMA in the lung fibroblasts revealed MMF could suppress the expression of α-SMA,but had no effect on the phenotype of myofibroblasts .The results of ELISA showed that the levels of CTGF and FN were significantly decreased compar with that of control group and was concentration -de-pendent ( P<0.05 ) .Conclusion: MMF can prevent lung fibroblasts from transdifferentiating into myofibroblasts and inhibit the expressions of CTGF and FN ,suggesting that MMF has anti-fibrosis effect and one of the mechanisms is by suppressing the expressions of CTGF and FN.