PDGF-dependent β-catenin activation is associated with abnormal pulmonary artery smooth muscle cell proliferation in pulmonary arterial hypertension.

ABSTRACT: Pulmonary arterial hypertension (PAH) is characterized by excessive pulmonary arterial smooth muscle cells (PASMCs) growth, partially in response to PDGF-BB but whether this is dependent on β-catenin (βC) activation is unclear. Compared to healthy cells, PAH PASMCs demonstrate higher levels of proliferation both at baseline and with PDGF-BB that correlate with GSK3β dependent βC activation. We show that βC knockdown but not Wnt5a stimulation reduces PDGF-BB dependent growth and normalizes PAH PASMCs proliferation. These findings support that cross-talk between PDGF and Wnt signaling modulates PASMC proliferation and suggest that βC targeted therapies could treat abnormal vascular remodeling in PAH.

SUBMITTER: Takahashi J 

PROVIDER: S-EPMC4722963 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature