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

• Final Report Year: 2014

Final Report Abstract

We proposed to investigate the role of TRPV1 channels in ischemic acute kidney injury (AKI) in mice. Using Trpv1 and Trpv4 gene-deficient mice, we found that these two TRPV channels have unique sites of vasoregulatory function in the kidney with functional TRPV1 having a narrow, discrete distribution in the resistance vasculature and TRPV4 having more universal, widespread distribution along different vascular segments. We tested the role of TRPV1 channels in ischemia/reperfusion (I/R)-induced AKI by modulating these channels with capsaicin (TRPV1 agonist), capsazepine (TRPV1 antagonist) and using Trpv1-/- mice. We found that activation of TRPV1 channels ameliorates I/R-induced AKI, but inhibition of these channels does not affect the outcome of AKI. Our results may have clinical implications for long-term safety of renal denervation to treat resistant hypertension in man, with respect to the function of primary sensory nerves in the response of the kidney to ischemic stimuli.

Publications

• ulsatile atheroprone shear stress affects the expression of transient receptor potential channels in human endothelial cells. Hypertension. 59(6):1232-1240
  Thilo, Florian; Vorderwülbecke, Bernd J.; Marki, Alex; Krueger, Katharina; Liu, Ying; Baumunk, Daniel; Zakrzewicz, Andreas & Tepel, Martin
  
• Transient receptor potential vanilloid 1 (TRPV1), TRPV4, and the kidney. Acta Physiol (Oxf). 2013 Mar;207(3):546-64
  Kaßmann, M.; Harteneck, C.; Zhu, Z.; Nürnberg, B.; Tepel, M. & Gollasch, M.
  
• Calcium-activated potassium channels in ischemia reperfusion: a brief update. Front Physiol. 2014 Oct 6;5:381
  Tano, Jean-Yves & Gollasch, Maik
  
• Functional transient receptor potential vanilloid 1 and transient receptor potential vanilloid 4 channels along different segments of the renal vasculature. Acta Physiol (Oxf). 2014 Jul 29
  Chen, L.; Kaßmann, M.; Sendeski, M.; Tsvetkov, D.; Marko, L.; Michalick, L.; Riehle, M.; Liedtke, W. B.; Kuebler, W. M.; Harteneck, C.; Tepel, M.; Patzak, A. & Gollasch, M.
  
• Hypoxia and ischemia-reperfusion: a BiK contribution? Am J Physiol Heart Circ Physiol. 2014 Sep 15;307(6):H811-7
  Tano, Jean-Yves & Gollasch, Maik
  
• Role of TRPV1 channels in ischemia/reperfusion-induced acute kidney injury. PLoS One. 2014 Oct 17;9(10):e109842
  Chen, Lan; Markó, Lajos; Kaßmann, Mario; Zhu, Ye; Wu, Kaiyin & Gollasch, Maik