The outburst of renal inflammatory response has been found to be a crucial cause of acute kidney injury (AKI). Attenuating the renal inflammation is an effective way for AKI treatment. Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been proven to be an anti-inflammatory factor. However, the effect of MANF on renal inflammation induced by AKI is unknown. In this study, we have investigated the effect of mono-macrophage-derived MANF on AKI. We constructed the mono-macrophage-specific MANF knockout (Mø MANF-/-) mouse and used lipopolysaccharide (LPS) to induce AKI in wild-type (WT) and Mø MANF-/- mice. With mono-macrophage-specific MANF deficiency, Mø MANF-/- mice had a lower survival rate, more severe renal injury, and higher serum level of pro-inflammatory TNF-α after AKI was induced by LPS. Also, compared with WT mice, there were more M1 macrophages in renal tissues of Mø MANF-/- mice with LPS treatment, which might be attributed to the enhanced NF-κB activation in the renal microenvironment. Our study indicates the immunoregulatory role of mono-macrophage-derived MANF in the pathophysiological process of AKI, as well as the potential clinical application of MANF for AKI treatment.
Keywords: M1/M2 macrophages; acute kidney injury; mesencephalic astrocyte–derived neurotrophic factor; nuclear factor kappa B pathway.