TRANSFORMING GROWTH-FACTOR-BETA-1 MODULATES TYPE-II CELL FIBRONECTIN AND SURFACTANT PROTEIN-C EXPRESSION

Extracellular matrix (ECM) deposition by alveolar type II cells is imp ortant for repair of a damaged alveolar epithelium. Transforming growt h factor-beta (TGF-beta) is abundant in injured lung and has profound effects on ECM production and cell differentiation. We determined the effects of TGF-beta 1 on type II cell expression of fibronectin and su rfactant protein C (SP-C) in vitro. TGF-beta 1 increased the proportio n of type II cells with detectable mRNA for fibronectin from 9 to 68%, as demonstrated by in situ hybridization, and increased the fibronect in mRNA levels 10-fold. TGF-beta 1-treated cultures had increased immu nostaining for fibronectin and increased secretion of metabolically la beled fibronectin. A decreased proportion of type II cells treated wit h TGF-beta 1 had detectable mRNA for SP-C, and the abundance of this m essage per cell decreased to 25% of control values. No effects of TGF- beta 1 were noted on the proportion of cells that contained lamellar b odies, which was 87% in both groups. These data indicate that TGF-beta 1 regulates type II cell fibronectin protein and mRNA levels. In addi tion, the decreased abundance of SP-C mRNA suggests that TGF-beta 1 ma y also modulate type II cell differentiation in lung injury.