The Mechanism of Renal Cell Damage after Acute Kidney Injury (AKI): A Laboratory Animal Study

Abstract

Background: Renal ischemia-reperfusion injury (IRI) is a critical part of acute kidney injury (AKI), which is accompanied with macrophage polarization. Roquin-1 (RC3H1)-depleted macrophages were demonstrated to aggravate hepatic IRI, but its role in AKI is still unclear. The aim of this study was to investigate the underlying mechanism of AKI mediated by RC3H1. Methods: A number of laboratory techniques were applied, including Enzyme linked immunosorbent assay (ELISA), flow cytometry and western blot. Results: After inducing AKI, macrophage M1/M2 ratio was significantly elevated and RC3H1 expression was significantly reduced. The promoter region of RC3H1 was found to be highly methylated after AKI, which was mainly modified by the methyl-transferase DNA (Cytosine-5)-Methyltransferase 3A (DNMT3a). DNMT3a was significantly upregulated in the AKI mice. Overexpression of RC3H1 suppressed the positive regulation of Jag1 (Jagged Canonical Notch Ligand 1)/Notch1 (Notch Receptor 1)/Hes1 (Hes Family BHLH Transcription Factor 1) signaling by AP2 Associated Kinase 1 (AAK1), thus relieving AKI. Conclusions: AKI-induced DNMT3a upregulation inhibited the expression of RC3H1 by hypermethylation. The low level of RC3H1 promoted AAK1 messenger ribonucleic acid (mRNA) accumulation, further activated Jag1/Notch1/Hes1 signaling to facilitate M1 polarization of macrophages and aggravated AKI.