Sustained Smad2 Phosphorylation Is Required for Myofibroblast Transformation in Response to TGF-β

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disease characterized by parenchymal fibrosis and structural distortion of the lungs. IPF is believed to be a disorder of abnormal wound healing, wherein the initial trigger to the fibrotic response is injury to the alveolar epithelial cells, followed by an exuberant, nonresolving wound-healing response (1). Injury of alveolar epithelial cells results in the elaboration of a fibrinous matrix and activation of several profibrotic mediators, of which transforming growth factor β (TGF-β) is the most established. Lung-targeted overexpression of TGF-β results in the development of lung fibrosis in animals. Conversely, inhibition of TGF-β can inhibit in vivo fibrogenesis...