Endothelial platelet-derived growth factor-mediated activation of smooth muscle platelet-derived growth factor receptors in pulmonary arterial hypertension.

endothelial cell platelet-derived growth factor platelet-derived growth factorreceptor smooth muscle cell

Journal

Pulmonary circulation
ISSN: 2045-8932
Titre abrégé: Pulm Circ
Pays: United States
ID NLM: 101557243

Informations de publication

Date de publication:
Historique:
received: 08 05 2020
accepted: 15 07 2020
entrez: 9 12 2020
pubmed: 10 12 2020
medline: 10 12 2020
Statut: epublish

Résumé

Platelet-derived growth factor is one of the major growth factors found in human and mammalian serum and tissues. Abnormal activation of platelet-derived growth factor signaling pathway through platelet-derived growth factor receptors may contribute to the development and progression of pulmonary vascular remodeling and obliterative vascular lesions in patients with pulmonary arterial hypertension. In this study, we examined the expression of platelet-derived growth factor receptor isoforms in pulmonary arterial smooth muscle and pulmonary arterial endothelial cells and investigated whether platelet-derived growth factor secreted from pulmonary arterial smooth muscle cell or pulmonary arterial endothelial cell promotes pulmonary arterial smooth muscle cell proliferation. Our results showed that the protein expression of platelet-derived growth factor receptor α and platelet-derived growth factor receptor β in pulmonary arterial smooth muscle cell was upregulated in patients with idiopathic pulmonary arterial hypertension compared to normal subjects. Platelet-derived growth factor activated platelet-derived growth factor receptor α and platelet-derived growth factor receptor β in pulmonary arterial smooth muscle cell, as determined by phosphorylation of platelet-derived growth factor receptor α and platelet-derived growth factor receptor β. The platelet-derived growth factor-mediated activation of platelet-derived growth factor receptor α/platelet-derived growth factor receptor β was enhanced in idiopathic pulmonary arterial hypertension-pulmonary arterial smooth muscle cell compared to normal cells. Expression level of platelet-derived growth factor-AA and platelet-derived growth factor-BB was greater in the conditioned media collected from idiopathic pulmonary arterial hypertension-pulmonary arterial endothelial cell than from normal pulmonary arterial endothelial cell. Furthermore, incubation of idiopathic pulmonary arterial hypertension-pulmonary arterial smooth muscle cell with conditioned culture media from normal pulmonary arterial endothelial cell induced more platelet-derived growth factor receptor α activation than in normal pulmonary arterial smooth muscle cell. Accordingly, the conditioned media from idiopathic pulmonary arterial hypertension-pulmonary arterial endothelial cell resulted in more pulmonary arterial smooth muscle cell proliferation than the media from normal pulmonary arterial endothelial cell. These data indicate that (a) the expression and activity of platelet-derived growth factor receptor are increased in idiopathic pulmonary arterial hypertension-pulmonary arterial smooth muscle cell compared to normal pulmonary arterial smooth muscle cell, and (b) pulmonary arterial endothelial cell from idiopathic pulmonary arterial hypertension patients secretes higher level of platelet-derived growth factor than pulmonary arterial endothelial cell from normal subjects. The enhanced secretion (and production) of platelet-derived growth factor from idiopathic pulmonary arterial hypertension-pulmonary arterial endothelial cell and upregulated platelet-derived growth factor receptor expression (and function) in idiopathic pulmonary arterial hypertension-pulmonary arterial smooth muscle cell may contribute to enhancing platelet-derived growth factor/platelet-derived growth factor receptor-associated pulmonary vascular remodeling in pulmonary arterial hypertension.

Identifiants

DOI: 10.1177/2045894020948470 PMID: 33294172 PMC: PMC7707860
pubmed: 33294172
doi: 10.1177/2045894020948470
pii: 10.1177_2045894020948470
pmc: PMC7707860
doi:

Types de publication

Journal Article

Langues

eng

Pagination

2045894020948470

Subventions

Organisme : NHLBI NIH HHS
ID : R01 HL136603
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL141387
Pays : United States

Informations de copyright

© The Author(s) 2020.

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Auteurs

Kang Wu (K)

Departments of Medicine and Physiology, The University of Arizona, Tucson, USA.
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Haiyang Tang (H)

Departments of Medicine and Physiology, The University of Arizona, Tucson, USA.
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Ruizhu Lin (R)

Departments of Medicine and Physiology, The University of Arizona, Tucson, USA.
Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

Shane G Carr (SG)

Departments of Medicine and Physiology, The University of Arizona, Tucson, USA.

Ziyi Wang (Z)

Departments of Medicine and Physiology, The University of Arizona, Tucson, USA.
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Division of Pulmonary, Critical Care and Sleep Medicine (Section of Physiology), University of California, San Diego, La Jolla, USA.

Aleksandra Babicheva (A)

Departments of Medicine and Physiology, The University of Arizona, Tucson, USA.
Division of Pulmonary, Critical Care and Sleep Medicine (Section of Physiology), University of California, San Diego, La Jolla, USA.

Ramon J Ayon (RJ)

Departments of Medicine and Physiology, The University of Arizona, Tucson, USA.
Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, USA.

Pritesh P Jain (PP)

Departments of Medicine and Physiology, The University of Arizona, Tucson, USA.
Division of Pulmonary, Critical Care and Sleep Medicine (Section of Physiology), University of California, San Diego, La Jolla, USA.

Mingmei Xiong (M)

Departments of Medicine and Physiology, The University of Arizona, Tucson, USA.
Division of Pulmonary, Critical Care and Sleep Medicine (Section of Physiology), University of California, San Diego, La Jolla, USA.
Department of Critical Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Marisela Rodriguez (M)

Departments of Medicine and Physiology, The University of Arizona, Tucson, USA.
Division of Pulmonary, Critical Care and Sleep Medicine (Section of Physiology), University of California, San Diego, La Jolla, USA.

Shamin Rahimi (S)

Division of Pulmonary, Critical Care and Sleep Medicine (Section of Physiology), University of California, San Diego, La Jolla, USA.

Francesca Balistrieri (F)

Division of Pulmonary, Critical Care and Sleep Medicine (Section of Physiology), University of California, San Diego, La Jolla, USA.

Shayan Rahimi (S)

Division of Pulmonary, Critical Care and Sleep Medicine (Section of Physiology), University of California, San Diego, La Jolla, USA.

Daniela Valdez-Jasso (D)

Department of Bioengineering, University of California, San Diego, La Jolla, USA.

Tatum S Simonson (TS)

Division of Pulmonary, Critical Care and Sleep Medicine (Section of Physiology), University of California, San Diego, La Jolla, USA.

Ankit A Desai (AA)

Departments of Medicine and Physiology, The University of Arizona, Tucson, USA.
Department of Medicine, Indiana University, Indinappolis, IN, USA.

Joe G N Garcia (JGN)

Departments of Medicine and Physiology, The University of Arizona, Tucson, USA.
ORCID: 0000-0002-6934-0420

John Y-J Shyy (JY)

Division of Cardiovascular Medicine, University of California, San Diego, La Jolla, USA.

Patricia A Thistlethwaite (PA)

Department of Surgery, University of California, San Diego, La Jolla, USA.

Jian Wang (J)

Departments of Medicine and Physiology, The University of Arizona, Tucson, USA.
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Division of Pulmonary, Critical Care and Sleep Medicine (Section of Physiology), University of California, San Diego, La Jolla, USA.

Ayako Makino (A)

Departments of Medicine and Physiology, The University of Arizona, Tucson, USA.
Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, USA.
ORCID: 0000-0003-1259-8604

Jason X-J Yuan (JX)

Departments of Medicine and Physiology, The University of Arizona, Tucson, USA.
Division of Pulmonary, Critical Care and Sleep Medicine (Section of Physiology), University of California, San Diego, La Jolla, USA.

Classifications MeSH