2. Academic Validation
  3. Role of TRPC6 in kidney damage after acute ischemic kidney injury

Role of TRPC6 in kidney damage after acute ischemic kidney injury

  • Sci Rep. 2022 Feb 22;12(1):3038. doi: 10.1038/s41598-022-06703-9.
Zhihuang Zheng 1 2 3,  Dmitry Tsvetkov 4 5 6,  Theda Ulrike Patricia Bartolomaeus 2 7,  Cem Erdogan 8,  Ute Krügel 9,  Johanna Schleifenbaum 8,  Michael Schaefer 9,  Bernd Nürnberg 10,  Xiaoning Chai 9,  Friedrich-Alexander Ludwig 11,  Gabriele N'diaye 2 7,  May-Britt Köhler 2 7,  Kaiyin Wu 12,  Maik Gollasch 13 14 15,  Lajos Markó 16 17 18 19
Affiliations

Affiliations

  • 1 Department of Nephrology/Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany.
  • 2 Experimental and Clinical Research Center (ECRC), Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Charité Universitätsmedizin, Berlin, Germany.
  • 3 Department of Nephrology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • 4 Department of Nephrology/Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany. [email protected].
  • 5 Experimental and Clinical Research Center (ECRC), Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Charité Universitätsmedizin, Berlin, Germany. [email protected].
  • 6 Department of Geriatrics, University of Greifswald, University District Hospital Wolgast, Greifswald, Germany. [email protected].
  • 7 Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
  • 8 Institute of Vegetative Physiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  • 9 Rudolf Boehm Institute for Pharmacology and Toxicology, Leipzig University, Leipzig, Germany.
  • 10 Department of Pharmacology, Experimental Therapy and Toxicology and Interfaculty Center of Pharmacogenomics and Drug Research, University of Tübingen, Tübingen, Germany.
  • 11 Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Leipzig, Germany.
  • 12 Department of Pathology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  • 13 Department of Nephrology/Intensive Care, Charité - Universitätsmedizin Berlin, Berlin, Germany. [email protected].
  • 14 Experimental and Clinical Research Center (ECRC), Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Charité Universitätsmedizin, Berlin, Germany. [email protected].
  • 15 Department of Geriatrics, University of Greifswald, University District Hospital Wolgast, Greifswald, Germany. [email protected].
  • 16 Experimental and Clinical Research Center (ECRC), Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Charité Universitätsmedizin, Berlin, Germany. [email protected].
  • 17 DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany. [email protected].
  • 18 Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany. [email protected].
  • 19 Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany. [email protected].
PMID: 35194063 DOI: 10.1038/s41598-022-06703-9
Abstract

Transient receptor potential channel subfamily C, member 6 (TRPC6), a non-selective cation channel that controls influx of Ca2+ and other monovalent cations into cells, is widely expressed in the kidney. TRPC6 gene variations have been linked to chronic kidney disease but its role in acute kidney injury (AKI) is unknown. Here we aimed to investigate the putative role of TRPC6 channels in AKI. We used Trpc6-/- mice and pharmacological blockade (SH045 and BI-749327), to evaluate short-term AKI outcomes. Here, we demonstrate that neither Trpc6 deficiency nor pharmacological inhibition of TRPC6 influences the short-term outcomes of AKI. Serum markers, renal expression of epithelial damage markers, tubular injury, and renal inflammatory response assessed by the histological analysis were similar in wild-type mice compared to Trpc6-/- mice as well as in vehicle-treated versus SH045- or BI-749327-treated mice. In addition, we also found no effect of TRPC6 modulation on renal arterial myogenic tone by using blockers to perfuse isolated kidneys. Therefore, we conclude that TRPC6 does not play a role in the acute phase of AKI. Our results may have clinical implications for safety and health of humans with TRPC6 gene variations, with respect to mutated TRPC6 channels in the response of the kidney to acute ischemic stimuli.

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