Integrins represent the main cell surface receptors that mediate cell-matrix and cell-cell interactions. They play critical roles in adhesion, migration, morphogenesis, and the differentiation of several cell types. Previous studies have demonstrated that members of the fibroblast growth factor (FGF)-2, transforming growth factor (TGF)-β1, and insulin growth factor (IGF)-1 play important roles in lens biology. In particularly, TGF-β1 appears to play a key role in extracellular matrix production, cell proliferation, and cell differentiation of lens epithelial cells. In this study we investigated the effects of FGF-2, TGF-β1, and IGF-1 on the modulation of integrin receptors using lens epithelial cell lines (HLE B-3 and αTN-4) and lens explants. We found that the expression of integrin α6 is downregulated by TGF-β1, but is not responsive to FGF-2 or IGF-1. The promoter activity of the integrin α6 gene decreased upon TGF-β1 treatment in a transient transfection assay, and flow cytometric analysis demonstrated the reduced expression of integrin α6 by TGF-β1, whereas significant changes were not observed in the level of integrin α6 after the addition of FGF-2. These findings suggest that the reduced expression of integrin α6 caused by TGF-β1 might play a role in the activation of the cell cycle genes required during the fiber differentiation of the lens. © 2001 Academic Press.