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

• Antragsteller: Professor Dr. Maik Gollasch
• Fachliche Zuordnung: Nephrologie
• Förderung: Förderung von 2011 bis 2013
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 152203169

• Erstellungsjahr: 2014

Zusammenfassung der Projektergebnisse

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.

Projektbezogene Publikationen (Auswahl)

• ulsatile atheroprone shear stress affects the expression of transient receptor potential channels in human endothelial cells. Hypertension. 59(6):1232-1240
  Thilo F, Vorderwulbecke BJ, Marki A, Krueger K, Liu Y, Baumunk D, Zakrzewicz A, Tepel M
  
• 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 JY, Gollasch M
  
• 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 WB, Kuebler WM, 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 JY, Gollasch M
  
• Role of TRPV1 channels in ischemia/reperfusion-induced acute kidney injury. PLoS One. 2014 Oct 17;9(10):e109842
  Chen L, Markó L, Kaßmann M, Zhu Y, Wu K, Gollasch M