The growth and maturation of the type II alveolar epithelial cell plays a key role in fetal lung development. Not only have several growth factors and hormones (EGF, retinoic acid, glucocorticoids and TGF-beta) been documented to impact upon the functional differentiation of the type II pneumocyte, the extracellular matrix (ECM) has also been demonstrated to profoundly influence the functional properties of this cell type. furthermore, the same recognized mediators of type II cell differentiation are also known regulators of ECM production. It is the hypothesis of this proposal that an interrelationship exists between soluble mediators and matrix biosynthesis, and that the former factors influence, at least in part, the functional properties of the type II alveolar epithelial cell by affecting the matrix phenotype of this cell. To test this hypothesis, we have been examining the effects of EGF, retinoic acid and TGF-beta and different matrices (type I collagen and matrigel) on the growth, culture morphology and collagen production in a possible cell culture model (FRLE cells) of the fetal type II pneumocyte. It is the purpose of this proposal to extend our observations to examine the effects of these soluble factors, as well as dexamethasone, and different matrices on the expression of differentiated functions (disaturated phosphatidylcholine and SP-A synthesis, expression of alkaline phosphatase and lysozyme, production of cell surface lectins (Maclura pomifera agglutinin (MPA) and Ricinus communis I (RCI) lectin), and collagen biosynthesis) by FRLE cells, to partially identify the matrix components responsible for expression of these differentiated functions, and to establish the effects of matrix on the response of FRLE cells to these soluble factors. These studies should provide further insight into the nature of FRLE cells, the mechanisms of cell-matrix interactions and the possible mediators of type II cell development under normal and pathological conditions.
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