VSIG4 overexpression alleviates acute kidney injury of mice via inhibition of M1-macrophages activation

Background: The infiltration and activation of M1-macrophages can promote renal tubular interstitial damage. The study aimed to investigate the effect of VSIG4 on M1-macrophages activation and acute kidney injury (AKI) mice. Methods: The M1-macrophage markers cluster of differentiation 86 (CD86) and inducible nitric oxide synthase (iNOS) were detected via flow cytometry. Cell viability and expression of inflammatory factors were analyzed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), 5-Ethynyl-2???-deoxyuridine (EdU), as well as quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) assays. Moreover, HK-2 cells stimulated with lipopolysaccharide (LPS) and RAW264.7 cells overexpressing V-set and immunoglobulin domain containing 4 (VSIG4) were co-cultured to analyze the effect of VSIG4 suppressing M1-macrophage activation on HK-2 cells via detecting cell proliferation and apoptosis levels. Furthermore, the pathological changes and iNOS expression of kidney tissue in VSIG4knockoutmice with renal ischemia-reperfusion injury (IRI) were detected by hematoxylin and eosin (H&E) and immunohistochemistry (IHC) staining. Results: Overexpression ofVSIG4 partially reversed the phenomenon of M1-macrophageactivation caused by LPS-upregulated CD86 and iNOS expression, reduced cell viability, and induced the expression levels of interleukin 1?? (IL-1??), interleukin 6 (IL-6), and tumor necrosis factor-?? (TNF-??) in RAW264.7. In addition, RAW264.7 cells overexpressing VSIG4 could also alleviate the low proliferation and high apoptotic level of HK-2 cells stimulated with LPS. After VSIG4 knockout, the kidney tissue of AKI mice showed obvious lesions and iNOS expression, indicating that VSIG4 knockout promoted the infiltration of M1-macrophages in the damaged kidney tissue and accelerated kidney tissue lesions. Conclusions: Overexpression of VSIG4 might alleviate the lesions of kidney tissue in AKI mice via inhibition of the secretion of inflammatory factors in M1-macrophages.