The protective effect of cGAS/STING/IFN-Ⅰ signaling pathway mediating endothelial progenitor cells on atherosclerosis associated with systemic lupus erythematosus
Objective To study the inhibitory effect of endothelial progenitor cells(EPCs)on aortic injury in mice with systemic lupus erythematosus(SLE)arteriosclerosis.Methods APOE-/-mice were injected with norphytane and high fat diet to establish lupus vascular injury model.Then the mice were divided into normal control group(ND group),high fat diet group(HFD group),high fat diet+SLE vascular injury group(HFD+SLE group),high fat diet+SLE vascular injury+hydroxychloroquine treatment group(HFD+SLE+Hydro group),high fat diet+SLE vascular injury+EPCs treatment group(HFD+SLE+EPCs group).At the end of the experiment,urine,blood and aortic tissues of mice in each group were collected,and the content of urinary protein and the depth of serum type Ⅰ interferon(IFN-Ⅰ)were detected by enzyme linked immunosorbent assay(ELISA).The activation of cyclic guanosine monophosphate synthase/interferon gene stimulating factor/type Ⅰ interferon(cGAS/STING/IFN-Ⅰ)pathway,the levels of inflammatory factors,adhesion fractions and chemokines in the aorta of mice in each group were detected by immunohistochemistry and Western blotting(WB).The lipid deposition in the aorta was detected by oil red staining.Results The results of ELISA showed that the levels of urinary protein and serum IFN-Ⅰ in HFD+SLE group were higher than those in normal control group.EPCs treatment could reduce the levels of urinary protein and serum IFN-Ⅰ in SLE atherosclerotic mice.WB results showed that the expression of CD19,CD68,CD34,chemokine,cGAS,p-STING,phosphorylated TANK binding kinase 1(p-TBK1),phosphorylated interferon regulatory factor 3(p-IRF3)and IFN-Ⅰ increased in HFD+SLE group,and hydroxychloroquine and EPCs decreased the levels of these factors.CGAS/STING/IFN-Ⅰ signal pathway is involved in the occurrence and development of atherosclerosis in SLE patients;both EPCs and hydroxychloroquine can inhibit the activation of cGAS/STING/IFN-Ⅰ signal,thus reducing atherosclerosis in SLE mice.Conclusions cGAS/STING/IFN-Ⅰ pathway is involved in the development of SLE atherosclerosis.EPCs can inhibit the activation of cGAS/STING signal,reduce the expression and secretion of IFN-Ⅰ,and then reduce vascular inflammation and inhibit the development of SLE-related atherosclerosis.
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