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PAX5/ITGAX Contributed to the Progression of Atherosclerosis by Regulation of B Differentiation via TNF-α Signaling Pathway.
DNA and Cell Biology 2023 Februrary 3
To investigate the effect of paired box protein 5 (PAX5)/integrin subunit alpha X (ITGAX) in atherosclerosis (AS). AS model was established using ApoE-/- mice (C57BL/6). Human vascular smooth muscle cells (HVSMCs) were stimulated with ox-LDL. Quantitative reverse transcription polymerase chain reaction and Western blotting were used to detect the expression levels of genes and proteins. Reporter constructs and luciferase assays were used to investigate the role of ITGAX and PAX5. Cells proliferation and inflammation factors were detected. The results presented that aortic plaque area, lipid content, serum triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels were significantly increased in the high-fat diet group ( p < 0.05). ITGAX was upregulated in atherosclerotic tissues. In addition, ox-LDL treatment induced HVSMCs proliferation, migration, and invasion. Reporter constructs and luciferase assays indicated ITGAX interaction with PAX5. Furthermore, siITGAX and siPAX5 cotransfection restored the rate of HVSMCs in G1 and S and G2/M phases, decreased the content of tumor necrosis factor-alpha (TNF-ɑ), interleukin (IL)-6, and IL-8 ( p < 0.05). Interestingly, siITGAX and siPAX5 cotransfection also decreased the expression levels of TNF-α, TNF-R1, TNF-R2, CD19, and CD86 ( p < 0.05). Our results suggest that ITGAX may be a potential therapeutic target for AS.
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