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Kidney Week

Abstract: TH-PO084

Deficiency of IKKα in Macrophages Mitigate the Fibrosis Progression of Kidney After Renal Ischemia-Reperfusion Injury

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Zhang, Feng, Nanjing Medical University, Nanjing, China
  • Wan, Xin, Nanjing First Hospital, Nanjing, China
Background

Acute kidney injury (AKI) could lead to chronic kidney disease (CKD) and the macrophages play key roles in this process. The aim of this study was to the discovery the role of IκB kinase α (IKKα) in macrophages in the process of AKI-to-CKD transition.

Methods

We crossed lyz2-Cre mice with IKKa floxed mice to generate mice with IKKα ablation in macrophage (Mac IKKa-/-). Mice renal ischemia/reperfusion injury (IRI) model was induced by clamping the renal artery for 45 min. Treated mice were evaluated for blood biochemistry, tissue histopathology and epithelial mesenchymal transition (EMT) markers. Macrophages isolated from peritoneal cavity for co-culturing with tubular epithelial cells (TEC)and flow cytometry analysis.

Results

We found that mice with Mac IKKa-/- significantly alleviated the fibrosis and ameliorated the kidney function loss after IRI compare with wide type (WT) mice. The expression of EMT markers and the infiltration of M2 macrophages were decreased in kidneys of Mac IKKa-/- mice after IRI. The in vitro experiment showed that the IRI TECs co-cultured with IKKa-/- macrophages (KO MΦ) downregulated the EMT accompany with downregulating Wnt/β-catenin signal.

Conclusion

These data support the hypothesis that IKKα was involved in mediating the macrophage polarization and elevating the fibrotic promoting inflammatory factor in macrophages. So knockdown the IKKα in macrophage may be a potential method that can be used to alleviate the AKI-to-CKD transition after IRI.