Regulatory RNases in acute kidney injury and AKI/CKD transition

• Applicant: Professor Dr. Hans-Joachim Anders
• Subject Area: Nephrology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 554613516

Acute kidney injury (AKI) and transition to chronic kidney disease (AKI/CKD transition) are accompanied by inflammatory reactions that play a key role in determining the course and long-term prognosis. We distinguish between necroinflammation in AKI, the resolution or persistence of inflammation in the transition from AKI to CKD and immune reactions during tissue remodeling in progressive CKD. In the field of immunology, the regulation of inflammatory reactions via RNA-binding proteins that influence RNA stability has been of great interest for several years, because only a small part of the transcribed RNA is translated into biologically active proteins. In this project, the role of the RNA-binding protein Regnase-3 (Reg3), as well as its interaction and redundancy with Reg1 in acute and chronic kidney diseases will be investigated in more detail using various mouse lines with cell type-specific deficiency for Reg, Reg1 and Reg1/3. We will investigate the cell type-specific expression of Regnases in samples of AKI (IA) in mice using single-cell transcriptome analysis. To investigate the role of Reg3 and Reg 1 in resident and infiltrating immune cells, we will induce AKI (IB) and AKI/CKD transition (IIB) in RANKCre:cReg3KO, Reg1KO, Reg1/3KO and WT mice and evaluate it multidimensionally. To investigate the role of Reg3 and Reg1 in tubular epithelial cells, we will conduct AKI (IC) and AKI/CKD transition (IIC) experiments and analyses in Pax8:cReg3KO, Reg1KO and Reg1/3KO and WT mice. In vitro experiments with primary cells from these mouse lines will mechanistically elucidate the findings. Against the background of promising preliminary data, this project will elucidate the importance of RNA stability in gene regulation in AKI and AKI/CKD transition.

• DFG Programme: Research Grants