Molecular physiology and epigenetics of NF-kB/BMP interactions in the post-ischemic kidney

• Applicants: Professor Dr. Dominik N. Müller; Professor Dr. Kai Schmidt-Ott; Dr. Ruth Ingeborg Schmidt-Ullrich
• Subject Area: Nephrology
• Term: from 2011 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 152203169

Acute kidney injury (AKI) is frequently caused by transient renal tissue hypoxia, which affects both tubular epithelial and vascular compartments. However, the specific and individual contribution these compartments as well as the compartment-specific molecular regulators remain poorly delineated. In the present project, we will investigate the role of nuclear factor-κB (NF-κB) and bone morphogenic protein (BMP) signaling and their potential molecular interaction during the pathogenesis of AKI. We provide preliminary evidence for activation and crosstalk between these two signaling pathways during the early post-ischemic phase in a mouse model of ischemic AKI. We further plan to use mouse mutants with vascular- or tubular-specific deficiency in NF-κB or BMP signaling to identify the individual contributions of these pathways, thereby dissecting the individual roles of the vascular and tubular compartments. Factors known to establish and maintain renal tissue damage, including tubular responses (apoptosis, proliferation), immune cell infiltration and hemodynamics will be analyzed. These studies will advance our understanding on the basic molecular mechanisms of AKI and, more generally, on the compartmental crosstalk. Our ultimate aim is to identify potential novel molecular targets for the prevention and treatment of AKI.

• DFG Programme: Research Units
• Subproject of: FOR 1368: Hemodynamic Mechanisms of Acute Kidney Injury