Differential modulation of integrin receptors and extracellular matrix laminin by transforming growth factor-beta 1 in rat alveolar epithelial cells.

The transforming growth factors-beta (TGFs-beta) family of genes plays important roles in cell growth and differentiation in many cell types. TGF beta modulates the synthesis and accumulation of extracellular matrix (ECM) components and the expression of cell surface receptors for ECM components. TGF beta 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 TGF beta 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 TGF beta on modulation of laminin and its integrin receptors alpha 6 beta 1 and alpha 3 beta 1 in lung alveolar epithelial cells, a rat alveolar type II cell-derived cell line, LM5, was incubated with TGF beta 1 (0-100 pg/ml) in serum-free medium for 0-16 h. We examined the expression of integrin subunits and laminin beta 2 chain (s-laminin) mRNAs and protein expression. By Northern blot analysis, TGF beta 1 induced dose-dependent increases in alpha 6 and beta 1 mRNA levels. TGF beta 1 also increased the expression of laminin beta 2 chain mRNA at 12-16 h poststimulation. In contrast, TGF beta 1 decreased alpha 3 mRNA expression. Immunoprecipitation studies of TGF beta 1-treated cells showed increased surface expression of both alpha 6 and beta 1 protein while surface expression of the alpha 3 integrin subunit was decreased. The same treatment resulted in increased laminin protein expression. These data suggest that TGF beta 1 may regulate alveolar epithelial cell differentiation in part through its modulation of integrins and laminin chains.