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

IF 5.8 2区医学 Q1 Medicine

Respiratory Research Pub Date : 2024-12-19 DOI:10.1186/s12931-024-03068-7

Yunwei Chen, Ningxin Liu, Yunjing Yang, Lingzhi Yang, Yan Li, Zhuo Qiao, Yumin Zhang, Ailing Li, Rui Xiang, Li Wen, Wei Huang

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引用次数: 0

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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NCAM1调节肺动脉高压患者肺动脉平滑肌细胞的增殖和迁移。

背景：肺动脉高压（Pulmonary hypertension， PH）是一种以肺动脉重塑为特征的恶性血管疾病。神经细胞粘附分子1 （NCAM1）是一种细胞表面糖蛋白，与包括心血管疾病在内的多种疾病有关。然而，NCAM1在PH中的作用仍未得到充分研究。方法：建立大鼠肺动脉高压模型和小鼠缺氧模型。采用ELISA法测定患者和大鼠血浆中NCAM1蛋白水平。采用qRT-PCR、Western blotting和免疫荧光法检测NCAM1在大鼠肺组织中的表达。用PDGF-BB刺激大鼠肺动脉平滑肌细胞，研究NCAM1对平滑肌细胞的影响。结果：在PH患者和单苦杏仁碱诱导的PH大鼠中均观察到NCAM1蛋白和mRNA水平升高。NCAM1敲低可改善缺氧诱导的PH，突出其在肺动脉重塑中的作用。在PASMCs中，PDGF-BB刺激可上调NCAM1的表达，增强细胞增殖和迁移。这种作用被NCAM1敲除减弱，但被ERK1/2通路激活剂（叔丁基对苯二酚，TBHQ）部分恢复，这表明NCAM1通过ERK1/2信号通路参与PASMC动力学。结论：我们的研究结果证实了NCAM1在肺动脉高压中的作用，并通过ERK1/2信号通路促进PASMC的增殖和迁移。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Respiratory Research RESPIRATORY SYSTEM-

CiteScore

9.70

自引率

1.70%

发文量

314

审稿时长

4-8 weeks

期刊介绍： Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases. As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion. Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.