Expression of the integrin alpha 8 beta 1 during pulmonary and hepatic fibrosis

The fibrotic response after diverse forms of injury is characterized by the accumulation of extracellular matrix proteins, proliferation of myofibrobl ast-like cells, and organ contraction. Myofibroblasts are key effector cell s in the development of the fibrotic response. They contribute to fibrosis through both increased cell number (proliferation) and enhanced matrix synt hesis, integrins, a class of cell adhesion molecules, are mediators of cell -extracellular matrix protein interactions that are important in the prolif erative and migratory response of cells to matrix proteins. We have previou sly cloned the human integrin subunit alpha 8, documented its high expressi on in lung tissue, and established it as a receptor for the matrix proteins fibronectin, vitronectin, and tenascin, We now demonstrate that alveolar i nterstitial cells are the primary cell type expressing alpha 8 beta 1 in th e lung parenchyma, Expression of alpha 8 beta 1 is concentrated primarily a long the thinned extensions of cells and at the tips of filopodia, Because of its unique distribution in alveolar interstitial cells, we hypothesized that it may play a role in the fibrotic response after injury, In bleomycin -induced pulmonary fibrosis, there is increased expression of alpha 8 beta 1 by interstitial fibroblasts, the majority of which coexpress alpha smooth muscle actin, a marker of tissue myofibroblasts, To establish a more gener al role for alpha 8 beta 1 during organ fibrosis, we further examined its e xpression in two rat models of liver fibrosis. During hepatic injury due to either carbon tetrachloride injury or bile duct ligation,we demonstrate de novo expression of alpha 8 beta 1 in activated hepatic stellate cells, the myofibroblast equivalent in liver, Taken together, the data localize alpha 8 beta 1 to myofibroblast-like cells during wound healing and suggest that signal transduction through the alpha 8 beta 1 integrin may contribute to the fibrotic response of organs to injury.