Using a basic cell biologic approach to elucidate the pathophysiology of BPD based on evolved cell-physiologic principles, we have determined the paracrine cell/molecular mechanism by which stretch coordinates epithelial-mesenchymal signaling, upregulating key genes for the induction of the prohomeostatic lipofibroblast phenotype—including PPARγ, ADRP, and leptin—and the retrograde stimulation of ATII cell surfactant phospholipid and protein synthesis by the lipofibroblast product leptin. This evidence concerns the gene LEP and bronchopulmonary dysplasia.