Inhibition of Myofibroblast Apoptosis by Transforming Growth Factor β1

Fibroblast differentiation to the myofibroblast phenotype is associated with α–smooth-muscle actin (α-SMA) expression and regulated by cytokines. Among these, transforming growth factor (TGF)-β1 and interleukin (IL)-1β can stimulate and inhibit myofibroblast differentiation, respectively. IL-1β inhibits α-SMA expression by inducing apoptosis selectively in myofibroblasts via induction of nitric oxide synthase (inducible nitric oxide synthase [iNOS]). Because TGF-β is known to inhibit iNOS expression, this study was undertaken to see if this cytokine can protect against IL-1β–induced myofibroblast apoptosis. Rat lung fibroblasts were treated with IL-1β and/or TGF-β1 and examined for expression of α-SMA, iNOS, and the apoptotic regulatory proteins bax and bcl-2. The results show that TGF-β1 caused a virtually complete suppression of IL-1β–induced iNOS expression while preventing the decline in α-SMA expression or the myofibroblast subpopulation. TGF-β1 treatment also completely suppressed the IL-1β–induced ...

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