Extracellular matrix biosynthesis by cultured fetal rat lung epithelial cells. II. Effects of acute exposure to epidermal growth factor and retinoic acid on collagen biosynthesis.

The effects of acute exposure to epidermal growth factor (EGF), retinoic acid, and EGF + retinoic acid on collagen biosynthesis by fetal rat lung epithelial (FRLE) have been evaluated. Acute exposure to either EGF or retinoic acid resulted in a small increase in the amount of radioactive substrate incorporated into total proteins, but simultaneous exposure to EGF + retinoic acid increased total protein synthesis approximately 2-fold. Quantitative evaluation of the genetic types of collagen synthesized by FRLE cells (types I, III, IV, and V) revealed that each experimental condition affected collagen production in a different manner. Acute exposure to EGF selectively inhibited type III collagen production, minimally affected type I and type IV collagen synthesis, but enhanced type V collagen production. Acute exposure to retinoic acid minimally affected type III production but slightly enhanced the synthesis of type I molecules. Simultaneous acute exposure to both EGF and retinoic acid significantly increased the amounts of types I, IV, and V collagen synthesized but minimally affected type III collagen production. Evaluation of the molecular forms of type I collagen (the type I-heterotrimer-molecular composition [alpha 1 (I)]2 alpha 2(I) and the type I-homotrimer-molecular composition [alpha 1 (I)]3) synthesized under each condition revealed that EGF minimally affected the production of either molecular form of type I collagen. In contrast, acute exposure to retinoic acid in the absence or presence of EGF caused a greater than 2-fold increase in the amount of type I-homotrimers synthesized but substantially decreased the amount of type I-heterotrimers produced. These results demonstrate that alone, either EGF or retinoic acid modulate collagen synthesis by FRLE cells and that in combination, these substances exert effects on collagen production that differ from their individual actions. Thus, in addition to documenting that EGF and retinoic acid modulate collagen biosynthesis in a cell line derived from the fetal type II pneumocyte, these studies establish that FRLE cells constitute a useful in vitro model system for investigating the regulation of matrix biosynthesis and its relationship to the development of the alveolar epithelial cell.