Regulation and Relevance of Myofibroblast Responses in Idiopathic Pulmonary Fibrosis

Curr Pathobiol Rep. 2013 Sep;1(3):199-208. doi: 10.1007/s40139-013-0017-8.


Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, incurable lung disease of unknown etiology with only limited treatment options. Current paradigms of disease pathogenesis feature recurrent or prolonged epithelial injury and an ensuing inflammatory response that culminates in the appearance of activated myofibroblasts. These cells are believed central to the excessive deposition of extracellular matrix that eventually obliterates the alveolar space to cause respiratory failure. Because the factors driving the accumulation of myofibroblasts remain poorly understood, effective therapies remain elusive. This review focuses on recent understanding of myofibroblasts including their seemingly uncontrolled proliferation and survival, their controversial origin in pathological IPF tissues, and the local biochemical and biomechanical matrix factors that drive their behavior. In addition, novel antifibrotics under development for the treatment of lung disease will be discussed. As our understanding of fibroblast and myofibroblast biology regulation expands, these cells may prove to be effective therapeutic targets.

Keywords: Idiopathic pulmonary fibrosis (IPF); extracellular matrix; fibroblast; fibrocytes; integrin; macrophage; mechanotransduction; myofibroblast; pathobiology.