Open Access

ARTICLE

Semaphorin 7A promotes human vascular smooth muscle cell proliferation and migration through the β-catenin signaling pathway

XIAOSU SONG, FEN GAO, HONG LI, WEIWEI QIN, CHANJUAN CHAI, GUOJUAN SHI, HUIYU YANG^*

Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, China

* Corresponding Author: HUIYU YANG. Email:

(This article belongs to this Special Issue: Biochemical and Epigenetics Changes in Health and Disease)

BIOCELL 2023, 47(4), 849-858. https://doi.org/10.32604/biocell.2023.026545

Received 12 September 2022; Accepted 28 November 2022; Issue published 08 March 2023

Abstract

Background: Vascular smooth muscle cells (VSMCs) undergo a conversion from a contractile phenotype to a proliferative synthetic phenotype, contributing to the pathogenesis of cardiovascular diseases. Semaphorin 7A (SEMA7A) is a glycosylphosphatidylinositol-anchored membrane protein that plays an important role in vascular homeostasis by regulating endothelial cell behaviors. However, the expression and role of SEMA7A in VSMCs remain unclear.Methods: In this study, we screened for VSMC-regulating genes in publicly available datasets and analyzed the expression of SEMA7A in human coronary artery smooth muscle cells (hCASMCs) treated with platelet-derived growth factor-BB (PDGF-BB). The effects of SEMA7A overexpression and knockdown on hCASMC proliferation and migration were examined. The signaling pathways involved in the action of SEMA7A in hCASMCs were determined.Results: Bioinformatic analysis showed that SEMA7A was significantly dysregulated in VSMCs treated with oxidized low-density lipoprotein or overexpressing progerin, a pro-atherogenic gene. The PDGF-BB stimulation led to a concentration- and time-dependent induction of SEMA7A. Depletion of SEMA7A attenuated PDGF-BB-induced hCASMC proliferation and migration. Conversely, overexpression of SEMA7A enhanced hCASMC proliferation and migration. Mechanistically, SEMA7A stimulated the activation of the β-catenin pathway and upregulated c-Myc, CCND1, and MMP7. Knockdown of β-catenin impaired SEMA7A-induced hCASMC proliferation and migration.Conclusions: SEMA7A triggers phenotype switching in VSMCs through the β-catenin signaling pathway and may serve as a potential therapeutic target for cardiovascular diseases.

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