Endothelial platelet-derived growth factor-mediated activation of smooth muscle platelet-derived growth factor receptors in pulmonary arterial hypertension
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 va...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-09-01
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| Series: | Pulmonary Circulation |
| Online Access: | https://doi.org/10.1177/2045894020948470 |
| _version_ | 1818119201216266240 |
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| author | Kang Wu Haiyang Tang Ruizhu Lin Shane G. Carr Ziyi Wang Aleksandra Babicheva Ramon J. Ayon Pritesh P. Jain Mingmei Xiong Marisela Rodriguez Shamin Rahimi Francesca Balistrieri Shayan Rahimi Daniela Valdez-Jasso Tatum S. Simonson Ankit A. Desai Joe G.N. Garcia John Y.-J. Shyy Patricia A. Thistlethwaite Jian Wang Ayako Makino Jason X.-J. Yuan |
| author_facet | Kang Wu Haiyang Tang Ruizhu Lin Shane G. Carr Ziyi Wang Aleksandra Babicheva Ramon J. Ayon Pritesh P. Jain Mingmei Xiong Marisela Rodriguez Shamin Rahimi Francesca Balistrieri Shayan Rahimi Daniela Valdez-Jasso Tatum S. Simonson Ankit A. Desai Joe G.N. Garcia John Y.-J. Shyy Patricia A. Thistlethwaite Jian Wang Ayako Makino Jason X.-J. Yuan |
| author_sort | Kang Wu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T05:06:26Z |
| format | Article |
| id | doaj.art-e8aacfe17c21472f9cda3af4d960ce7d |
| institution | Directory Open Access Journal |
| issn | 2045-8940 |
| language | English |
| last_indexed | 2024-12-11T05:06:26Z |
| publishDate | 2020-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pulmonary Circulation |
| spelling | doaj.art-e8aacfe17c21472f9cda3af4d960ce7d2022-12-22T01:20:01ZengWileyPulmonary Circulation2045-89402020-09-011010.1177/2045894020948470Endothelial platelet-derived growth factor-mediated activation of smooth muscle platelet-derived growth factor receptors in pulmonary arterial hypertensionKang Wu0Haiyang Tang1Ruizhu Lin2Shane G. Carr3Ziyi Wang4Aleksandra Babicheva5Ramon J. Ayon6Pritesh P. Jain7Mingmei Xiong8Marisela Rodriguez9Shamin Rahimi10Francesca Balistrieri11Shayan Rahimi12Daniela Valdez-Jasso13Tatum S. Simonson14Ankit A. Desai15Joe G.N. Garcia16John Y.-J. Shyy17Patricia A. Thistlethwaite18Jian Wang19Ayako Makino20Jason X.-J. Yuan21State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of , Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of , Guangzhou, ChinaDepartment of Genetics and Endocrinology, Guangzhou Women and Children’s Medical Center, , Guangzhou, ChinaDepartments of Medicine and Physiology, The University of Arizona, Tucson, USADivision of Pulmonary, Critical Care and Sleep Medicine (Section of Physiology), University of California, San Diego, La Jolla, USADivision of Pulmonary, Critical Care and Sleep Medicine (Section of Physiology), University of California, San Diego, La Jolla, USADepartment of Molecular Physiology and Biological Physics, , Charlottesville, USADivision of Pulmonary, Critical Care and Sleep Medicine (Section of Physiology), University of California, San Diego, La Jolla, USADepartment of Critical Medicine, The Third Affiliated Hospital of , Guangzhou, ChinaDivision of Pulmonary, Critical Care and Sleep Medicine (Section of Physiology), University of California, San Diego, La Jolla, USADivision of Pulmonary, Critical Care and Sleep Medicine (Section of Physiology), University of California, San Diego, La Jolla, USADivision of Pulmonary, Critical Care and Sleep Medicine (Section of Physiology), University of California, San Diego, La Jolla, USADivision of Pulmonary, Critical Care and Sleep Medicine (Section of Physiology), University of California, San Diego, La Jolla, USADepartment of Bioengineering, University of California, San Diego, La Jolla, USADivision of Pulmonary, Critical Care and Sleep Medicine (Section of Physiology), University of California, San Diego, La Jolla, USADepartment of Medicine, Indiana University, Indinappolis, IN, USADepartments of Medicine and Physiology, The University of Arizona, Tucson, USADivision of Cardiovascular Medicine, University of California, San Diego, La Jolla, USADepartment of Surgery, University of California, San Diego, La Jolla, USADivision of Pulmonary, Critical Care and Sleep Medicine (Section of Physiology), University of California, San Diego, La Jolla, USADivision of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, La Jolla, USADivision of Pulmonary, Critical Care and Sleep Medicine (Section of Physiology), University of California, San Diego, La Jolla, USAPlatelet-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.https://doi.org/10.1177/2045894020948470 |
| spellingShingle | Kang Wu Haiyang Tang Ruizhu Lin Shane G. Carr Ziyi Wang Aleksandra Babicheva Ramon J. Ayon Pritesh P. Jain Mingmei Xiong Marisela Rodriguez Shamin Rahimi Francesca Balistrieri Shayan Rahimi Daniela Valdez-Jasso Tatum S. Simonson Ankit A. Desai Joe G.N. Garcia John Y.-J. Shyy Patricia A. Thistlethwaite Jian Wang Ayako Makino Jason X.-J. Yuan Endothelial platelet-derived growth factor-mediated activation of smooth muscle platelet-derived growth factor receptors in pulmonary arterial hypertension Pulmonary Circulation |
| title | Endothelial platelet-derived growth factor-mediated activation of smooth muscle platelet-derived growth factor receptors in pulmonary arterial hypertension |
| title_full | Endothelial platelet-derived growth factor-mediated activation of smooth muscle platelet-derived growth factor receptors in pulmonary arterial hypertension |
| title_fullStr | Endothelial platelet-derived growth factor-mediated activation of smooth muscle platelet-derived growth factor receptors in pulmonary arterial hypertension |
| title_full_unstemmed | Endothelial platelet-derived growth factor-mediated activation of smooth muscle platelet-derived growth factor receptors in pulmonary arterial hypertension |
| title_short | Endothelial platelet-derived growth factor-mediated activation of smooth muscle platelet-derived growth factor receptors in pulmonary arterial hypertension |
| title_sort | endothelial platelet derived growth factor mediated activation of smooth muscle platelet derived growth factor receptors in pulmonary arterial hypertension |
| url | https://doi.org/10.1177/2045894020948470 |
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