Transient receptor potential vanilloid type 1 (TRPV1) channels in acute kidney injury

• Applicant: Professor Dr. Maik Gollasch
• Subject Area: Nephrology
• Term: from 2011 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 152203169

The transient receptor potential vanilloid type 1 (TRPV1) channel is a ligand-gated non selective cation channel that can be activated by endogenous substances including 20-hydroxyeicosatetraenoic acid (20-HETE) and exogenous substances including capsaicin, the pungent ingredient of red chilli pepper. We hypothesize that TRPV1 channels play crucial roles in ischemic AKI by modulating renal blood flow. TRPV1 channels and their natural activator 20-HETE may also contribute to vascular and tubular repair processes that allow a recovery of renal function after ischemia/reperfusion (I/R) -induced injury. Recent literature and own preliminary results indeed suggest an important role of TRPV1 channels and 20-HETE in the regulation of vascular tone in the setting of renal I/R injury, a model for acute kidney injury (AKI) used by four groups of the Research Unit. Capsaicin significantly increases I/Rdependent increase of TRPV1 mRNA expression in the specific kidney regions. Here we evaluate the role of TRPV1 in I/R-dependent AKI, its regulation by vascular factors with major focus at 20-HETE and other CYP-eicosanoids. To this end we test (i) drugs that specifically target TRPV1 channels, (ii) knockout and transgenic mice with genetically modified TRPV1 channel expression and (iii) drugs that specifically target the synthesis and action of 20-HETE or epoxyeicosanoic acids (EETs). As endpoints we analyze I/R-induced expression and function of TRPV1 channels, renal dysfunction and tubular injury.

• DFG Programme: Research Units
• Subproject of: FOR 1368: Hemodynamic Mechanisms of Acute Kidney Injury
• Participating Person: Professor Dr. Martin Ernst Tepel