1. RGC-32' dual role in smooth muscle cells and atherogenesis.
- Author
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Vlaicu SI, Tatomir A, Fosbrink M, Nguyen V, Boodhoo D, Cudrici C, Badea TC, Rus V, and Rus H
- Subjects
- Cells, Cultured, Complement System Proteins, Endothelial Cells, Humans, Myocytes, Smooth Muscle metabolism, Transforming Growth Factor beta, Atherosclerosis, Cell Cycle Proteins genetics, Cell Cycle Proteins metabolism, Complement Membrane Attack Complex metabolism, Muscle Proteins genetics, Muscle Proteins metabolism, Nerve Tissue Proteins genetics, Nerve Tissue Proteins metabolism
- Abstract
Proliferation of endothelial cells (EC) and smooth muscle cells (SMC) is a critical process in atherosclerosis. Here, we investigated the involvement of sublytic C5b-9 effector Response Gene to Complement 32 (RGC-32) in cell cycle activation, phenotypic switch, and production of extracellular matrix (ECM) in SMC. Overexpression of RGC-32 augmented C5b-9-induced cell cycle activation and proliferation of SMC in an ERK1-dependent manner and silencing of RGC-32 inhibited C5b-9-induced cell cycle activation. C5b-9-induced cell cycle activation also required phosphorylation of RGC-32 at threonine 91. We found that ECM components fibronectin and collagens I-V were expressed by SMC in human aortic atherosclerotic tissue. Silencing of RGC-32 in cultured SMC was followed by a significant reduction in TGF-β-induced expression of SMC differentiation markers myocardin, SM22 and α-SMA, and that of collagens I, IV and V. These data suggest that RGC-32 participates in both sublytic C5b-9-induced cell cycle activation and TGF-β-induced ECM production., (Published by Elsevier Inc.)
- Published
- 2022
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