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 m atrix (ECM) components and the expression of cell surface receptors fo r ECM components. TGF beta is increased in alveolar lining fluid durin g inflammatory reactions of the lung and has been identified in alveol ar epithelial cells of developing lungs and hyperplastic type II cells during repair. However, little is known about how TGF beta may regula te expression of extracellular matrix proteins and ECM receptors in lu ng alveolar epithelial cells, Laminin, a major glycoprotein component of epithelial basement membrane, is synthesized and secreted by alveol ar 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-der ived cell line, LM5, was incubated with TGF beta(1) (0-100 pg/ml) in s erum-free medium for 0-16 h, We examined the expression of integrin su bunits and laminin beta 2 chain (s-laminin) mRNAs and protein expressi on, By Northern blot analysis, TGF beta(1) induced dose-dependent incr eases 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, Immunop recipitation studies of TGF beta(1)-treated cells showed increased sur face expression of both alpha(6) and alpha(3) protein while surface ex pression of the alpha(3) integrin subunit was decreased, The same trea tment resulted in increased laminin protein expression, These data sug gest that TGF beta(1) may regulate alveolar epithelial cell differenti ation in part through its modulation of integrins and laminin chains. (C) 1995 Academic Press, Inc.