Extracellular matrix biosynthesis by cultured fetal rat lung epithelial cells. IV. Effects of chronic exposure to retinoic acid on growth, differentiation, and collagen biosynthesis.

Effects of chronic exposure to retinoic acid on a cell line (FRLE cells) established from the fetal rat lung type II alveolar epithelial cell have been studied. Chronic exposure to retinoic acid inhibited proliferation and altered the pattern of culture morphology at the light microscopic level. At the ultrastructural level, the development of lamellar body-like structures was inhibited. Although the rates of both total collagen and protein produced per cell were enhanced by chronic retinoic acid exposure, the increase in collagen production exceeded that of total protein synthesis. Chromatographic evaluation of collagen types I, III, IV, and V revealed increases in the amounts of radioactivity incorporated into each collagen type. However, the magnitudes of the increases differed for each collagen type, with the production of type IV collagen being the most enhanced. These analyses also indicated several additional effects on collagen production: 1) collagen type specific alterations in the ratio of secreted to cell associated molecules, 2) an increased ratio of type I homotrimers to type I heterotrimers, and 3) a decreased ratio of type V homotrimers to type V heterotrimers. These results indicate that chronic exposure to retinoic acid selectively affects collagen production in and differentiation of FRLE cells and establish that these changes are opposite to those observed under conditions of chronic exposure to EGF.