Foam Cell-Derived CXCL14 Muti-Functionally Promotes Atherogenesis and Is a Potent Therapeutic Target in Atherosclerosis
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CXC chemokine family has been related to atherogenesis for long. However, the relationship between CXCL14 and atherogenesis is still unclear. This study preliminarily detected CXCL14 expression at foam cells in atherosclerosis specimens by immunohistochemistry. In vitro foam cells were derived from THP-1 after phorbol-12-myristate-13-acetate (PMA) and oxidized low-density lipoprotein (ox-LDL) stimulation. Immunoblotting and qPCR convinced CXCL14 expression variation during foam cell formation. We further demonstrated that ox-LDL regulated CXCL14 expression by AP-1. AP-1 could bind to CXCL14 promoter and up-regulate CXCL14 mRNA expression. Besides, CXCL14 promoted THP-1 migration, macrophage lipid phagocytosis, and smooth muscle cell migration as well as proliferation mainly via the ERK1/2 pathway. Additionally, a CXCL14 peptide-induced immune therapy showed efficacy in ApoE−/− mouse model. In conclusion, our study demonstrated that CXCL14 is highly up-regulated during foam cell formation and promotes atherogenesis in various ways. CXCL14 may be a potent therapeutic target for atherosclerosis.
KeywordsFoam cell Atherogenesis CXCL14
W.T., R.Y., C.P., and Y.W. conducted the experiments. Y.D. analyzed the results. W.T. wrote the manuscript. Z.H. and G.W. conceived the experiments. All authors reviewed the manuscript.
This study was supported in part by research grants 81770263, 81570254, and 31271040 from the National Natural Science Foundation of China.
Compliance with Ethical Standards
All experimental protocols were approved by the Ethical Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. All animal studies were performed in accordance with the Guidelines of the Hubei Council of Animal Care and approved by the Experimental Animal Committee of the Huazhong University of Science and Technology in China. The informed consent was obtained from all subjects, and this study is approved by the Ethical Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.
The authors declare that they have no competing interests.
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