Pleiotrophin Regulates Alveolar Epithelial Cell Differentiation During Fetal Lung Development

Pleiotrophin (PTN) is a cytokine highly expressed at the late stage of embryogenesis. It plays important roles in angiogenesis, mesenchymal‐epithelial interaction, cell differentiation and migration. Our previous studies have shown that PTN was highly expressed in fetal lungs and located in mesenchymal cells adjacent to the developing epithelium. We further investigated the roles of PTN in fetal lung development and alveolar epithelial cell differentiation using fetal lung organ culture and isolated fetal lung epithelial cells. PTN expression in fetal lung organ culture was knocked down by an adenoviral vector carrying siRNA targeted to PTN. The reduction of PTN had little effects on the branching morphogenesis of fetal lungs. However, the SP‐C mRNA and protein levels were markedly decreased in the siRNA treated lungs. Additionally, when isolated fetal alveolar epithelial type II cells were cultured on plastic dishes, PTN arrested the trans‐differentiation of type II cells to type I cells. Our study suggested that PTN may have important roles in the regulation of fetal lung development and alveolar epithelial cell trans‐differentiation. (Supported by AHA 0610143Z, NIH R01 HL‐52146, R01 HL‐071628 and R01 HL‐083188).