Abrogation of TGF-beta1-induced fibroblast-myofibroblast differentiation by histone deacetylase inhibition.

ABSTRACT: Idiopathic pulmonary fibrosis (IPF) is a devastating disease with no known effective pharmacological therapy. The fibroblastic foci of IPF contain activated myofibroblasts that are the major synthesizers of type I collagen. Transforming growth factor (TGF)-beta1 promotes differentiation of fibroblasts into myofibroblasts in vitro and in vivo. In the current study, we investigated the molecular link between TGF-beta1-mediated myofibroblast differentiation and histone deacetylase (HDAC) activity. Treatment of normal human lung fibroblasts (NHLFs) with the pan-HDAC inhibitor trichostatin A (TSA) inhibited TGF-beta1-mediated alpha-smooth muscle actin (alpha-SMA) and alpha1 type I collagen mRNA induction. TSA also blocked the TGF-beta1-driven contractile response in NHLFs. The inhibition of alp

SUBMITTER: Guo W 

PROVIDER: S-EPMC2777501 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature