VEGF induces airway epithelial cell proliferation in human fetal lung in vitro

Vascular endothelial growth factor (VEGF) is a potent endothelial cell mito gen involved in normal and abnormal angiogenesis. VEGF mRNA and protein are abundant in distal epithelium of midtrimester human fetal lung. In the pre sent study, we identified immunoreactivity for KDR, a major VEGF-specific r eceptor, in distal lung epithelial cells of human fetal lung tissue, sugges ting a possible autocrine or paracrine regulatory role for VEGF in pulmonar y epithelial cell growth and differentiation. Addition of exogenous VEGF to human fetal lung explants resulted in increased epithelium volume density and lumen volume density in the tissues, both morphometric parameters of ti ssue differentiation. Cellular proliferation demonstrated by bromodeoxyurid ine uptake was prominent in distal airway epithelial cells and increased in the VEGF-treated explants. VEGF-treated explants also demonstrated increas ed surfactant protein (SP) A mRNA, SP-C mRNA, and SP-A protein levels compa red with controls. However, SP-B mRNA levels were unaffected by VEGF treatm ent. [H-3]choline incorporation into total phosphatidyleholine was increase d by VEGF treatment, but incorporation into disaturated phosphatidylcholine was not affected by exogenous VEGF. Based on these observations, we conclu de that VEGF may be an important autocrine growth factor for distal airway epithelial cells in the developing human lung.