Differential Modulation of Integrin Receptors and Extracellular Matrix Laminin by Transforming Growth Factor-β1 in Rat Alveolar Epithelial Cells

Abstract The transforming growth factors-β (TGFs-β) family of genes plays important roles in cell growth and differentiation in many cell types. TGFβ modulates the synthesis and accumulation of extracellular matrix (ECM) components and the expression of cell surface receptors for ECM components. TGFβ is increased in alveolar lining fluid during inflammatory reactions of the lung and has been identified in alveolar epithelial cells of developing lungs and hyperplastic type II cells during repair. However, little is known about how TGFβ may regulate expression of extracellular matrix proteins and ECM receptors in lung alveolar epithelial cells. Laminin, a major glycoprotein component of epithelial basement membrane, is synthesized and secreted by alveolar epithelial cells. To study the effects of TGFβ on modulation of laminin and its integrin receptors α 6 β 1 and α 3 β 1 in lung alveolar epithelial cells, a rat alveolar type II cell-derived cell line, LM5, was incubated with TGFβ 1 (0-100 pg/ml) in serum-free medium for 0-16 h. We examined the expression of integrin subunits and laminin β2 chain (s-laminin) mRNAs and protein expression. By Northern blot analysis, TGFβ 1 induced dose-dependent increases in α 6 and β 1 mRNA levels. TGFβ 1 also increased the expression of laminin β2 chain mRNA at 12-16 h poststimulation. In contrast, TGFβ decreased α 3 mRNA expression. Immunoprecipitation studies of TGFβ 1 -treated cells showed increased surface expression of both α 6 and β 1 protein while surface expression of the α 3 integrin subunit was decreased. The same treatment resulted in increased laminin protein expression. These data suggest that TGFβ 1 may regulate alveolar epithelial cell differentiation in part through its modulation of integrins and laminin chains.