PCSK3 inhibits cell migration by regulating the inflammatory response of vascular smooth muscle cells and the expression of cell phenotype transformation markers
CHEN Naxia, QI Miaomiao, LIN Hengxiu, HUANG Shan
The First Affiliated Hospital of Hainan Medical University, Haikou 571001, China
Abstract：Objective To investigate the effect of Recombinant Proprotein Convertase Subtilisin/Kexin Type 3(PCSK3) on the proliferation and migration of vascular smooth muscle cells. Methods First, the cell model was established by stimulating vascular smooth muscle cells (VSMCs) of mouse with 0, 25, 50, 100 mg/L ox-LDL, and the expression of PCSK3 mRNA was detected by RT-PCR. The atherosclerotic model cells stimulated by 100 mg/L ox-LDL were used as the model group, VSMCs were divided into NC group (0 mg/L ox-LDL stimulated VSMCs+scramble siRNA, SCR), ox-LDL group (model group+SCR), ox LDL+si-PCSK3 1 # group (model group+si-PCSK3 1 # plasmid) and ox-LDL+si-PCSK3 2 # group (model group+si-PCSK3 2 # plasmid). The proliferation activity of VSMCs in each group was detected by EdU method, and cell migration was observed by Transwell, ELISA kit for detecting IL-1 β, TNF α, IL-6, intercellular adhesion molecule-1(ICAM-1) content, RT-PCR was used to detect the changes of mRNA expression of type I and ⅲ collagen and smooth muscle actin (α-SMA) in SMC cells of each group. Results Under the concentration of 100 mg/L ox-LDL treatment, PCSK3 in VSMCs significantly increased, which can induce the proliferation of VSMCs. Interference with the endogenous expression of PCSK3 can inhibit the migration and proliferation ability of VSMCs stimulated by ox-LDL, reduce the secretion of IL-1 β, TNF α, IL-6, and ICAM-1 levels. Compared with the ox-LDL group, the expression of type I collagen and OPN mRNA was significantly downregulated in the si-PCSK3 treated cell group, while the expression of α-SMA mRNA was significantly upregulated. Conclusion Down-regulation of PCSK3 can attenuate the proliferation and migration of vascular smooth muscle cells, which may be related to the regulation of PCSK3 on intracellular inflammatory response and cell phenotype transformation.
2023, Vol. 20 
