NCAM1 Promotes the Proliferation and Migration of Pulmonary Arterial Smooth Muscle Cells via the ERK1/2 Pathway

Background: Pulmonary arterial hypertension (PAH) 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 relationship between NCAM1 and PAH is unknown. Methods: : Enzyme-linked immunosorbent assay, Bioinformatics methods, Echocardiography, Right heart catheterization, Hematoxylin-eosin staining, Immunofluorescent staining, Quantitative reverse transcription polymerase chain reaction, Western blotting, Cell Counting Kit-8, EdU staining, Scratch wound healing assay and Transwell migration assay were used to elucidate the role of NCAM1 in PAH. Results: : The protein expression levels of NCAM1 were increased in the plasma of PAH patients. Using bioinformatics methods, we found that the transcript levels of NCAM1 were also upregulated in the lung tissues of PAH patients. The expression levels of NCAM1 protein in the plasma of MCT-induced PAH rats were also increased. We found that both NCAM1 protein and mRNA expression levels were significantly enhanced in MCT rat lung tissues. Furthermore, we found that NCAM1 mRNA and protein levels were significantly upregulated in PDGF-BB-treated PASMCs. NCAM1 knockdown could partially reverse PDGF-BB-induced proliferation and migration of PASMCs. However, the effects were partially restored by tert-butylhydroquinone (TBHQ), an ERK1/2 activator. And recombinant rat NCAM1 protein promotes PASMC proliferation and migration and activates the ERK1/2 signaling pathway. Conclusion: Our findings suggest that NCAM1 may be associated with pulmonary arterial hypertension and promotes the proliferation and migration of PASMCs via the ERK1/2 signaling pathway.