Focal segmental glomerulosclerosis (FSGS) is a common and progressive form of kidney injury for which treatment options are limited. New findings from a study in animal models of FSGS suggest that a small molecule inhibitor of the TRPC5 ion channel could provide therapeutic benefit.
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Brown, E. J., Pollak, M. R. & Barua, M. Genetic testing for nephrotic syndrome and FSGS in the era of next-generation sequencing. Kidney Int. 85, 1030–1038 (2014).
Reiser, J. et al. TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function. Nat. Genet. 37, 739–744 (2005).
Winn, M. P. et al. A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis. Science 308, 1801–1804 (2005).
Schaldecker, T. et al. Inhibition of the TRPC5 ion channel protects the kidney filter. J. Clin. Invest. 123, 5298–5309 (2013).
Zhou, Y. et al. A small-molecule inhibitor of TRPC5 ion channels suppresses progressive kidney disease in animal models. Science 358, 1332–1336 (2017).
Tian, D. et al. Antagonistic regulation of actin dynamics and cell motility by TRPC5 and TRPC6 channels. Sci. Signal. 3, ra77 (2010).
Wang, X. et al. TRPC5 does not cause or aggravate glomerular disease. J. Am. Soc. Nephrol. https://doi.org/10.1681/ASN.2017060682 (2017).
Ilatovskaya, D. V. et al. Podocyte injury in diabetic nephropathy: implications of angiotensin II-dependent activation of TRPC channels. Sci. Rep. 5, 17637 (2015).
Ilatovskaya, D. V. & Staruschenko, A. TRPC6 channel as an emerging determinant of the podocyte injury susceptibility in kidney diseases. Am. J. Physiol. Renal Physiol. 309, F393–F397 (2015).
Bröker-Lai, J. et al. Heteromeric channels formed by TRPC1, TRPC4 and TRPC5 define hippocampal synaptic transmission and working memory. EMBO J. 36, 2770–2789 (2017).
J.v.d.W. is supported by the European Union's Horizon 2020 Marie Skłodowska-Curie actions (grant agreement no. 748058).
The authors declare no competing financial interests.
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van der Wijst, J., Bindels, R. TRPC5 inhibition to treat progressive kidney disease. Nat Rev Nephrol 14, 145–146 (2018). https://doi.org/10.1038/nrneph.2018.4
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