TRPC6 channel as an emerging determinant of the podocyte injury susceptibility in kidney diseases

Am J Physiol Renal Physiol. 2015 Sep 1;309(5):F393-7. doi: 10.1152/ajprenal.00186.2015. Epub 2015 Jun 17.


Podocytes (terminally differentiated epithelial cells of the glomeruli) play a key role in the maintenance of glomerular structure and permeability and in the incipiency of various renal abnormalities. Injury to podocytes is considered a major contributor to the development of kidney disease as their loss causes proteinuria and progressive glomerulosclerosis. The physiological function of podocytes is critically dependent on proper intracellular calcium handling; excessive calcium influx in these cells may result in the effacement of foot processes, apoptosis, and subsequent glomeruli damage. One of the key proteins responsible for calcium flux in the podocytes is transient receptor potential cation channel, subfamily C, member 6 (TRPC6); a gain-of-function mutation in TRPC6 has been associated with the onset of the familial forms of focal segmental glomerulosclerosis (FSGS). Recent data also revealed a critical role of this channel in the onset of diabetic nephropathy. Therefore, major efforts of the research community have been recently dedicated to unraveling the TRPC6-dependent effects in the initiation of podocyte injury. This mini-review focuses on the TRPC6 channel in podocytes and colligates recent data in an attempt to shed some light on the mechanisms underlying the pathogenesis of TRPC6-mediated glomeruli damage and its potential role as a therapeutic target for the treatment of chronic kidney diseases.

Keywords: TRPC6; diabetic nephropathy; glomerulosclerosis; glomerulus; intracellular calcium; podocyte; proteinuria.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Diabetic Nephropathies / genetics
  • Diabetic Nephropathies / metabolism*
  • Diabetic Nephropathies / pathology
  • Disease Susceptibility
  • Glomerulosclerosis, Focal Segmental / genetics
  • Glomerulosclerosis, Focal Segmental / metabolism*
  • Glomerulosclerosis, Focal Segmental / pathology
  • Humans
  • Kidney Diseases / genetics
  • Kidney Diseases / metabolism*
  • Kidney Diseases / pathology
  • Mutation
  • Podocytes / metabolism*
  • Podocytes / pathology
  • Signal Transduction
  • TRPC Cation Channels / genetics
  • TRPC Cation Channels / metabolism*
  • TRPC6 Cation Channel


  • TRPC Cation Channels
  • TRPC6 Cation Channel
  • TRPC6 protein, human