Protective role of Trpc6 knockout in the progression of diabetic kidney disease

Denisha Spires, Daria V. Ilatovskaya, Vladislav Levchenko, Paula E. North, Aron M. Geurts, Oleg Palygin, Alexander Staruschenko

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Diabetic kidney disease (DKD) is a chronic kidney pathology that leads to end-stage renal disease. Previous studies from our laboratory indicate that there is an association between the development of DKD and the transient receptor potential canonical 6 (TRPC6) channel. Trpc6 expression and activity were increased in the streptozotocin (STZ)-treated Dahl Salt-sensitive (Dahl SS) rat, an established model of type 1 diabetes. Here, using a Trpc6 knockout created on the Dahl SS rat background (SSTrpc6-/-), we test the hypothesis that the absence of Trpc6 will protect podocytes and kidney function during the development of DKD. Four groups of animals (control SSWT, SSTrpc6-/-, STZ-treated SSWT, and STZSSTrpc6-/-) were utilized in this study. Diabetes development was monitored for 11 wk after STZ injection with periodic weight, glucose, and urinary output measurements. There was an increase in albuminuria and glomerular injury following STZ treatment, which was not different between Dahl SS and SSTrpc6-/- groups. Western blot analysis revealed elevated levels of nephrin in urine samples of STZ-SSWT rats, which was higher compared with STZ-SSTrpc6-/- rats. Furthermore, pathological increases in basal [Ca2+]i levels and foot process damage of podocytes during the development of DKD was attenuated in the STZ-SSTrpc6-/- compared with STZ-SSWT rats. Overall, our data indicate that TRPC6 channel inhibition may have at least partial renoprotective effects, which could lead to the development of new pharmacological tools to treat or prevent the progression of DKD.

Original languageEnglish (US)
Pages (from-to)F1091-F1097
JournalAmerican Journal of Physiology - Renal Physiology
Volume315
Issue number4
DOIs
StatePublished - Oct 2018
Externally publishedYes

Keywords

  • Diabetic kidney disease
  • Intracellular calcium
  • Podocytes
  • Trpc6

ASJC Scopus subject areas

  • Physiology
  • Urology

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