HHS Public Access Author manuscript Author Manuscript
FEBS Lett. Author manuscript; available in PMC 2017 January 08. Published in final edited form as: FEBS Lett. 2016 January ; 590(1): 101–109. doi:10.1002/1873-3468.12038.
PDGF-DEPENDENT β-CATENIN ACTIVATION IS ASSOCIATED WITH ABNORMAL PULMONARY ARTERY SMOOTH MUSCLE CELL PROLIFERATION IN PULMONARY ARTERIAL HYPERTENSION Jack Takahashi1,2,3, Mark Orcholski1,2,3, Ke Yuan1,2,3, and Vinicio de Jesus Perez1,2,3
Author Manuscript
1Division
of Pulmonary and Critical Care Medicine, Stanford University Medical Center, Stanford, California
2The
Vera Moulton Wall Center for Pulmonary Vascular Medicine, Stanford University Medical Center, Stanford, California
3Stanford
Cardiovascular Institute, Stanford University Medical Center, Stanford, California
Abstract
Author Manuscript
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 PDGFBB 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.
Keywords pulmonary hypertension; smooth muscle cells; Wnt signaling; PDGF; vascular remodeling; pulmonary disease
INTRODUCTION Author Manuscript
Pulmonary arterial hypertension (PAH) is a vascular disease characterized by a progressive increase in pulmonary vascular resistance that, if untreated, leads to right ventricular failure and premature death. PAH is attributed to the obstruction of small (
FEBS Lett. Author manuscript; available in PMC 2017 January 08. Published in final edited form as: FEBS Lett. 2016 January ; 590(1): 101–109. doi:10.1002/1873-3468.12038.
PDGF-DEPENDENT β-CATENIN ACTIVATION IS ASSOCIATED WITH ABNORMAL PULMONARY ARTERY SMOOTH MUSCLE CELL PROLIFERATION IN PULMONARY ARTERIAL HYPERTENSION Jack Takahashi1,2,3, Mark Orcholski1,2,3, Ke Yuan1,2,3, and Vinicio de Jesus Perez1,2,3
Author Manuscript
1Division
of Pulmonary and Critical Care Medicine, Stanford University Medical Center, Stanford, California
2The
Vera Moulton Wall Center for Pulmonary Vascular Medicine, Stanford University Medical Center, Stanford, California
3Stanford
Cardiovascular Institute, Stanford University Medical Center, Stanford, California
Abstract
Author Manuscript
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 PDGFBB 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.
Keywords pulmonary hypertension; smooth muscle cells; Wnt signaling; PDGF; vascular remodeling; pulmonary disease
INTRODUCTION Author Manuscript
Pulmonary arterial hypertension (PAH) is a vascular disease characterized by a progressive increase in pulmonary vascular resistance that, if untreated, leads to right ventricular failure and premature death. PAH is attributed to the obstruction of small (
