The proposed studies are specifically designed to test the following hypotheses: (1) stretch-initiated transduction in fetal type II cells triggers PTHrP production; (2) PTHrP stimulates fetal lung fibroblast maturation by receptor-dependent mechanisms; (3) PTHrP stimulates production of mesenchymal cytokines and growth factors which promote type II cell maturation. Elaboration of lipoprotein lipase, glucocorticoid receptor, and PTHrP-regulated fibroblast growth factors and cytokines by PTHrP-deficient lung tissue and fibroblasts will be studied at the mRNA and protein levels to determine which functions are affected in this model.
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