title: 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.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Stanford, CA, USA.|The Vera Moulton Wall Center for Pulmonary Vascular Medicine, Stanford, CA, USA.|Stanford Cardiovascular Institute, Stanford University Medical Center, CA, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Takahashi
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Stanford, CA, USA.|The Vera Moulton Wall Center for Pulmonary Vascular Medicine, Stanford, CA, USA.|Stanford Cardiovascular Institute, Stanford University Medical Center, CA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Orcholski
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Stanford, CA, USA.|The Vera Moulton Wall Center for Pulmonary Vascular Medicine, Stanford, CA, USA.|Stanford Cardiovascular Institute, Stanford University Medical Center, CA, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Yuan
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Stanford, CA, USA.|The Vera Moulton Wall Center for Pulmonary Vascular Medicine, Stanford, CA, USA.|Stanford Cardiovascular Institute, Stanford University Medical Center, CA, USA.
authors.forename: Vinicio
authors.initials: V
authors.lastname: de Jesus Perez
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000925:Anticoagulants / Q000494:pharmacology; D000077214:Becaplermin; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D065627:Familial Primary Pulmonary Hypertension / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011651:Pulmonary Artery / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects; D000071818:Wnt-5a Protein; D051176:beta Catenin / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D000925:Anticoagulants; C495270:CTNNB1 protein, human; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051176:beta Catenin; D000077214:Becaplermin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3
keywords: PDGF; Wnt signaling; pulmonary disease; pulmonary hypertension; smooth muscle cells; vascular remodeling