| First Author | Jain M | Year | 2021 |
| Journal | JCI Insight | Volume | 6 |
| Issue | 10 | PubMed ID | 34027892 |
| Mgi Jnum | J:322285 | Mgi Id | MGI:6753807 |
| Doi | 10.1172/jci.insight.147134 | Citation | Jain M, et al. (2021) Integrin alpha9 regulates smooth muscle cell phenotype switching and vascular remodeling. JCI Insight 6(10) |
| abstractText | Excessive proliferation of vascular smooth muscle cells (SMCs) remains a significant cause of in-stent restenosis. Integrins, which are heterodimeric transmembrane receptors, play a crucial role in SMC biology by binding to the extracellular matrix protein with the actin cytoskeleton within the SMC. Integrin alpha9 plays an important role in cell motility and autoimmune diseases; however, its role in SMC biology and remodeling remains unclear. Herein, we demonstrate that stimulated human coronary SMCs upregulate alpha9 expression. Targeting alpha9 in stimulated human coronary SMCs, using anti-integrin alpha9 antibody, suppresses synthetic phenotype and inhibits SMC proliferation and migration. To provide definitive evidence, we generated an SMC-specific alpha9-deficient mouse strain. Genetic ablation of alpha9 in SMCs suppressed synthetic phenotype and reduced proliferation and migration in vitro. Mechanistically, suppressed synthetic phenotype and reduced proliferation were associated with decreased focal adhesion kinase/steroid receptor coactivator signaling and downstream targets, including phosphorylated ERK, p38 MAPK, glycogen synthase kinase 3beta, and nuclear beta-catenin, with reduced transcriptional activation of beta-catenin target genes. Following vascular injury, SMC-specific alpha9-deficient mice or wild-type mice treated with murine anti-integrin alpha9 antibody exhibited reduced injury-induced neointimal hyperplasia at day 28 by limiting SMC migration and proliferation. Our findings suggest that integrin alpha9 regulates SMC biology, suggesting its potential therapeutic application in vascular remodeling. |
