αv integrins play an important role in myofibroblast differentiation

Abstract

Transforming growth factor-β1 is a potent mediator of the differentiation of fibroblasts into myofibroblasts, which is characterized by the appearance of the cytoskeletal protein α-smooth muscle actin. The aim of this study was to investigate the role of integrin extracellular matrix receptors in transforming growth factor-β1–induced myofibroblast differentiation. We show that blockade of the αv and/or β1 integrins prevents the transforming growth factor-β1–induced myofibroblast differentiation, seen by the increased expression of α-smooth muscle actin and enhanced collagen gel contraction in three human fibroblast cell lines (from the mouth, skin, and kidney). Further, blockade of αv specific integrins αvβ5 and αvβ3 suppressed myofibroblast differentiation in fibroblasts from the mouth and skin; however, in the kidney cells, the prevention of differentiation was seen only with blockade of αvβ5 integrin but not αvβ3. A possible reason for this result may be different degrees of responsiveness to transforming growth factor-β1 treatment seen from different anatomical origins of the cell lines. These data indicate a novel role for αv integrins in the differentiation of human fibroblasts from the mouth, skin, and kidney into myofibroblasts and suggest that there is a common differentiation pathway.