The role of cationic channels of the potential TRPC receptor in the pathogenesis of idiopathic nephrotic syndrome in children
https://doi.org/10.21508/1027-4065-2021-66-5-67-74
Abstract
Idiopathic nephrotic syndrome is the most common glomerulopathy in children, with a prevalence of approximately 16 per 100,000 of child population worldwide. Any chronic glomerular disease has the same type of development mechanism. Regardless of the damaging factor, after the death of a significant part of the nephrons, there occurs a steady decrease in the glomerular filtration rate, while morphologically we most often determine focal segmental glomerulosclerosis. Studying the causes of focal segmental glomerulosclerosis is an urgent problem in pediatric nephrology. Recently, there has been discussed the role of the cation channels of the potential receptor TRPC of podocytes in the development of proteinuria and focal segmental glomerulosclerosis. The article provides data on the role of TRPC receptors in the pathogenesis of focal segmental glomerulosclerosis. The authors present their our own data demonstrating gene expression of the cationic channels family of the potential receptor TRPC1, TRPC3, TRPC4, TRPC5 and TRPC6 in children with idiopathic nephrotic syndrome, depending on the morphological picture of the disease and sensitivity to steroid therapy.
Keywords
Supporting agencies: the work was carried out within the framework of funding from the State Assignment “Clinical and molecular genetic criteria for predicting the effectiveness of steroid and immunosuppressive therapy for primary nephrotic syndrome in children” No. 200080056
About the Authors
S. L. Morozov
Veltischev Research and Clinical Institute for Pediatrics at the Pirogov Russian National Research Medical University; Pirogov Russian National Research Medical University
Russian Federation
Russian Federation
Moscow
V. V. Dlin
Veltischev Research and Clinical Institute for Pediatrics at the Pirogov Russian National Research Medical University
Russian Federation
Russian Federation
Moscow
References
1. Eddy A.A., Symons J.M. Nephrotic syndrome in childhood. Lancet 2003; 362(9384): 629–639. DOI: 10.1016/S0140-6736(03)14184-0
2. Becherucci F., Roperto R.M., Materassi M., Romagnani P. Chronic kidney disease in children. Clin Kidney J 2016; 9(4):583–591. DOI: 10.1093/ckj/sfw047
3. Harambat .J, van Stralen K.J., Kim J.J., Tizard E.J. Epidemiology of chronic kidney disease in children. Pediatr Nephrol 2012; 27(3): 363–373. DOI: 10.1007/s00467-011-1939-1
4. Kriz W., Gretz N., Lemley K.V. Progression of glomerular diseases: Is the podocyte the culprit? Kidney Int 1998; 54(3):687–697. DOI: 10.1046/j.1523-1755.1998.00044.x
5. Pavenstädt H., Kriz W., Kretzler M. Cell biology of the glomerular podocyte. Physiol Rev 2003; 83(1): 253–307. DOI: 10.1152/physrev.00020.2002
6. Pollak M.R., Quaggin S.E., Hoenig M.P., Dworkin L.D. The glomerulus: the sphere of influence. Clin J Am Soc Nephrol 2014; 9(8): 1461–1469. DOI: 10.2215/CJN.09400913
7. Wiggins R.C. The spectrum of podocytopathies: a unifying view of glomerular diseases. Kidney Int 2007; 71(12): 1205–1214. DOI: 10.1038/sj.ki.5002222
8. Rosenberg A.Z., Kopp J.B. Focal Segmental Glomerulosclerosis. Clin J Am Soc Nephrol 2017; 12(3): 502–517. DOI: 10.2215/CJN.05960616
9. Gees M., Colsoul B., Nilius B. The role of transient receptor potential cation channels in Ca2+ signaling. Cold Spring Harb Perspect Biol 2010; 2(10): a003962. DOI: 10.1101/cshperspect.a003962
10. Nilius B., Owsianik G., Voets T., Peters J.A. Transient receptor potential cation channels in disease. Physiol Rev 2007; 87(1):165–217. DOI: 10.1152/physrev.00021.2006
11. Ding Y., Winters A., Ding M., Graham S., Akopova I., Muallem S. et al. Reactive oxygen species-mediated TRPC6 protein activation in vascular myocytes, a mechanism for vasoconstrictor-regulated vascular tone. J Biol Chem 2011; 286(36): 31799–31809. DOI: 10.1074/jbc.M111.248344
12. Kim E.Y., Anderson M., Wilson C., Hagmann H., Benzing T., Dryer S.E. NOX2 interacts with podocyte TRPC6 channels and contributes to their activation by diacylglycerol: essential role of podocin in formation of this complex. Am J Physiol Cell Physiol 2013; 305(9): 960–971. DOI: 10.1152/ajpcell.00191.2013
13. Winn M.P., Conlon P.J., Lynn K.L., Farrington M.K., Creazzo T., Hawkins A.F. et al. A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis. Science 2005; 308(5729): 1801–1804. DOI: 10.1126/science.1106215
14. Reiser J., Polu K.R., Möller CC, Kenlan P, Altintas MM, Wei C. et al. TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function. Nat Genet 2005; 37(7): 739–744. DOI: 10.1038/ng1592
15. Huber T.B., Schermer B., Müller R.U., Höhne M., Bartram M., Calixto A. et al. Podocin and MEC-2 bind cholesterol to regulate the activity of associated ion channels. Proc Natl Acad Sci USA 2006; 103(46): 17079–17086. DOI: 10.1073/pnas.0607465103
16. Zhu B., Chen N., Wang Z-H., Pan X-X., Ren H., Zhang W. et al. Identification and functional analysis of a novel TRPC6 mutation associated with late onset familial focal segmental glomerulosclerosis in Chinese patients. Mutat Res 2009; 664(1–2): 84–90. DOI: 10.1016/j.mrfmmm.2008.11.021
17. Büscher A.K., Konrad M., Nagel M., Witzke O., Kribben A., Hoyer P.F. et al. Mutations in podocyte genes are a rare cause of primary FSGS associated with ESRD in adult patients. Clin Nephrol 2012; 78(1): 47–53. DOI: 10.5414/cn107320
18. Heeringa S.F., Möller C.C.,Du J.,Yue L.,Hinkes B.,Chernin G. etal. A novel TRPC6 mutation that causes childhood FSGS. PLoS One 2009; 4(11): e7771. DOI: 10.1371/journal.pone.0007771
19. Wang L., Jirka G., Rosenberg P.B., Buckley A.F., Gomez J.A., Fields T.A. et al. Gq signaling causes glomerular injury by activating TRPC6. J Clin Invest 2015; 125(5): 1913–1926. DOI: 10.1172/JCI76767
20. Möller C.C., Flesche J., Reiser J. Sensitizing the Slit Diaphragm with TRPC6 ion channels. J Am Soc Nephrol 2009; 20(5): 950–953. DOI: 10.1681/ASN.2008030329
21. Möller C.C., Wei C., Altintas M.M., Li J., Greka A., Ohse T. et al. Induction of TRPC6 channel in acquired forms of proteinuric kidney disease. J Am Soc Nephrol 2007; 18(1): 29–36. DOI: 10.1681/ASN.2006091010
22. Krall P., Canales C.P., Kairath P., Carmona-Mora P., Molina J., Carpio J.D. et al. Podocyte-specific overexpression of wild type or mutant trpc6 in mice is sufficient to cause glomerular disease. PLoS One 2010; 5(9): e12859. DOI: 10.1371/journal.pone.0012859
23. Hogan P.G., Chen L., Nardone J., Rao A. Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev 2003;17(18):2205–2232. DOI: 10.1101/gad.1102703
24. Kuwahara K., Wang Y., McAnally J., Richardson J.A., Bassel-Duby R., Hill J.A. et al. TRPC6 fulfills a calcineurin signaling circuit during pathologic cardiac remodeling. J Clin Invest 2006; 116(12): 3114–3126. DOI: 10.1172/JCI27702
25. Li H., Rao A., Hogan P.G. Interaction of calcineurin with substrates and targeting proteins. Trends Cell Biol 2011;21(2):91–103. DOI: 10.1016/j.tcb.2010.09.011
26. Ilatovskaya D.V., Staruschenko A. TRPC6 channel as an emerging determinant of the podocyte injury susceptibility in kidney diseases. Am J Physiol Renal Physiol 2015; 309(5): F393–397. DOI: 10.1152/ajprenal.00186.2015
27. Saliba Y., Karam R., Smayra V., Aftimos G., Abramowitz J., Birnbaumer L. et al. Evidence of a Role for Fibroblast Transient Receptor Potential Canonical 3 Ca2+ Channel in Renal Fibrosis. J Am Soc Nephrol 2015; 26(8): 1855–1876. DOI: 10.1681/ASN.2014010065
Review
For citations:
Morozov S.L., Dlin V.V. The role of cationic channels of the potential TRPC receptor in the pathogenesis of idiopathic nephrotic syndrome in children. Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 2021;66(5):67-74. (In Russ.) https://doi.org/10.21508/1027-4065-2021-66-5-67-74
Views:
435
Email this article 