NCAM1 modulates the proliferation and migration of pulmonary arterial smooth muscle cells in pulmonary hypertension

Abstract Background Pulmonary hypertension (PH) is a malignant vascular disease characterized by pulmonary arterial remodeling. Neural cell adhesion molecule 1 (NCAM1) is a cell surface glycoprotein that is involved in a variety of diseases, including cardiovascular disease. However, the role of NCA...

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Main Authors: Yunwei Chen, Ningxin Liu, Yunjing Yang, Lingzhi Yang, Yan Li, Zhuo Qiao, Yumin Zhang, Ailing Li, Rui Xiang, Li Wen, Wei Huang
Format: Article
Language:English
Published: BMC 2024-12-01
Series:Respiratory Research
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Online Access:https://doi.org/10.1186/s12931-024-03068-7
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author Yunwei Chen
Ningxin Liu
Yunjing Yang
Lingzhi Yang
Yan Li
Zhuo Qiao
Yumin Zhang
Ailing Li
Rui Xiang
Li Wen
Wei Huang
author_facet Yunwei Chen
Ningxin Liu
Yunjing Yang
Lingzhi Yang
Yan Li
Zhuo Qiao
Yumin Zhang
Ailing Li
Rui Xiang
Li Wen
Wei Huang
author_sort Yunwei Chen
collection DOAJ
description Abstract Background Pulmonary hypertension (PH) is a malignant vascular disease characterized by pulmonary arterial remodeling. Neural cell adhesion molecule 1 (NCAM1) is a cell surface glycoprotein that is involved in a variety of diseases, including cardiovascular disease. However, the role of NCAM1 in PH remains underexplored. Methods Pulmonary hypertension models were established using monocrotaline in rats and hypoxia in mice. NCAM1 protein levels in plasma from patients and rats were measured by ELISA. Expression of NCAM1 in rat lung tissues were evaluated using qRT-PCR, Western blotting, and immunofluorescence. The effects of NCAM1 on rat pulmonary artery smooth muscle cells were studied by stimulating these cells with PDGF-BB. Results Elevated levels of NCAM1 protein and mRNA were observed in both PH patients and monocrotaline-induced PH rats. NCAM1 knockdown ameliorated hypoxia-induced PH, highlighting its role in pulmonary artery remodeling. In PASMCs, NCAM1 expression was upregulated by PDGF-BB stimulation, enhancing cell proliferation and migration. This effect was attenuated by NCAM1 knockdown but partially restored by an ERK1/2 pathway activator (tert-butylhydroquinone, TBHQ), suggesting NCAM1’s involvement in PASMC dynamics through the ERK1/2 signaling pathway. Conclusion Our findings confirm the role of NCAM1 in pulmonary arterial hypertension and demonstrate its promotion of PASMC proliferation and migration through the ERK1/2 signaling pathway.
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spelling doaj-art-d86b52aa675c42a184e9b1a911af4a352024-12-22T12:43:17ZengBMCRespiratory Research1465-993X2024-12-0125111510.1186/s12931-024-03068-7NCAM1 modulates the proliferation and migration of pulmonary arterial smooth muscle cells in pulmonary hypertensionYunwei Chen0Ningxin Liu1Yunjing Yang2Lingzhi Yang3Yan Li4Zhuo Qiao5Yumin Zhang6Ailing Li7Rui Xiang8Li Wen9Wei Huang10Department of Cardiology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Cardiology, The First Affiliated Hospital of Chongqing Medical UniversityAbstract Background Pulmonary hypertension (PH) is a malignant vascular disease characterized by pulmonary arterial remodeling. Neural cell adhesion molecule 1 (NCAM1) is a cell surface glycoprotein that is involved in a variety of diseases, including cardiovascular disease. However, the role of NCAM1 in PH remains underexplored. Methods Pulmonary hypertension models were established using monocrotaline in rats and hypoxia in mice. NCAM1 protein levels in plasma from patients and rats were measured by ELISA. Expression of NCAM1 in rat lung tissues were evaluated using qRT-PCR, Western blotting, and immunofluorescence. The effects of NCAM1 on rat pulmonary artery smooth muscle cells were studied by stimulating these cells with PDGF-BB. Results Elevated levels of NCAM1 protein and mRNA were observed in both PH patients and monocrotaline-induced PH rats. NCAM1 knockdown ameliorated hypoxia-induced PH, highlighting its role in pulmonary artery remodeling. In PASMCs, NCAM1 expression was upregulated by PDGF-BB stimulation, enhancing cell proliferation and migration. This effect was attenuated by NCAM1 knockdown but partially restored by an ERK1/2 pathway activator (tert-butylhydroquinone, TBHQ), suggesting NCAM1’s involvement in PASMC dynamics through the ERK1/2 signaling pathway. Conclusion Our findings confirm the role of NCAM1 in pulmonary arterial hypertension and demonstrate its promotion of PASMC proliferation and migration through the ERK1/2 signaling pathway.https://doi.org/10.1186/s12931-024-03068-7NCAM1PASMCsPDGF-BBERK1/2PH
spellingShingle Yunwei Chen
Ningxin Liu
Yunjing Yang
Lingzhi Yang
Yan Li
Zhuo Qiao
Yumin Zhang
Ailing Li
Rui Xiang
Li Wen
Wei Huang
NCAM1 modulates the proliferation and migration of pulmonary arterial smooth muscle cells in pulmonary hypertension
Respiratory Research
NCAM1
PASMCs
PDGF-BB
ERK1/2
PH
title NCAM1 modulates the proliferation and migration of pulmonary arterial smooth muscle cells in pulmonary hypertension
title_full NCAM1 modulates the proliferation and migration of pulmonary arterial smooth muscle cells in pulmonary hypertension
title_fullStr NCAM1 modulates the proliferation and migration of pulmonary arterial smooth muscle cells in pulmonary hypertension
title_full_unstemmed NCAM1 modulates the proliferation and migration of pulmonary arterial smooth muscle cells in pulmonary hypertension
title_short NCAM1 modulates the proliferation and migration of pulmonary arterial smooth muscle cells in pulmonary hypertension
title_sort ncam1 modulates the proliferation and migration of pulmonary arterial smooth muscle cells in pulmonary hypertension
topic NCAM1
PASMCs
PDGF-BB
ERK1/2
PH
url https://doi.org/10.1186/s12931-024-03068-7
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