Fig. 8.

Proposed model for CTGF inhibition of alveolarization and vascularization and induction of pulmonary hypertension in neonatal lungs. Overexpression of CTGF in AT II cells via an autocrine mechanism induces β-catenin nuclear translocation, and that may decrease VEGF expression in epithelium leading to decreased VEGFR2 phosphorylation in endothelium, thus disrupting alveolar and pulmonary vascular development. Epithelium-produced CTGF may also induce β-catenin nuclear translocation via a paracrine mechanism in pulmonary artery smooth muscle cells (PASMC), thus leading to excessive pulmonary vascular remodeling. The combination of poor alveolar and vascular development as well as increased vascular remodeling results in pulmonary hypertension. The CTGF-induced infiltration via β-catenin-dependent and/or independent mechanisms further disrupts alveolar and vascular development and induces pulmonary hypertension.