Role of TRPC6 in kidney damage after acute ischemic kidney injury.

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.

• Authors: Zhihuang Zheng, Dmitry Tsvetkov, Theda Ulrike Patricia Bartolomaeus, Cem Erdogan, Ute Krügel, Johanna Schleifenbaum, Michael Schaefer, Bernd Nürnberg, Xiaoning Chai, Friedrich-Alexander Ludwig, Gabriele N'diaye, May-Britt Köhler, Kaiyin Wu, Maik Gollasch, Lajos Markó
• Journal: Scientific reports (Sci Rep) Vol. 12 Issue 1 Pg. 3038 (02 22 2022) ISSN: 2045-2322 [Electronic] England
• PMID: 35194063 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• TRPC6 Cation Channel
• Trpc6 protein, mouse
• Calcium

Topics

• APACHE
• Acute Kidney Injury (genetics, pathology)
• Animals
• Calcium (metabolism)
• Genetic Variation
• Ischemia (genetics, pathology)
• Kidney (blood supply, metabolism)
• Mice, Transgenic
• Negative Results
• TRPC6 Cation Channel (genetics, physiology)