RGC-32′ dual role in smooth muscle cells and atherogenesis

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-8-induced expression of SMC differentiation markers myocardin, SM22 and alpha-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-8-induced ECM production.

Automated summary

In this study, the involvement of RGC-32 in cell proliferation and cell cycle activation in endothelial cells and smooth muscle cells in atherosclerosis was investigated. Overexpression of RGC-32 enhanced the cell cycle activation and proliferation induced by C5b-9, while silencing of RGC-32 inhibited this activation.