Podocyte injury in diabetic nephropathy: implications of angiotensin II-dependent activation of TRPC channels. Sci Rep 2015 Dec 10;5:17637
Date
12/15/2015Pubmed ID
26656101Pubmed Central ID
PMC4674698DOI
10.1038/srep17637Scopus ID
2-s2.0-84949591115 (requires institutional sign-in at Scopus site) 88 CitationsAbstract
Injury to podocytes is considered a major contributor to diabetic kidney disease: their loss causes proteinuria and progressive glomerulosclerosis. Podocyte depletion may result from improper calcium handling due to abnormal activation of the calcium permeant TRPC (Transient Receptor Potential Canonical) channels. Angiotensin II (Ang II) levels are found to be elevated in diabetes; furthermore, it was reported that Ang II causes activation of TRPC6 in podocytes. We hypothesized here that Ang II-mediated calcium influx is aggravated in the podocytes under the conditions of type 1 diabetic nephropathy (DN). Diabetes was induced in the Dahl Salt-Sensitive rats by an injection of streptozotocin (STZ-SS). Eleven weeks post treatment was sufficient for the animals to develop hyperglycemia, excessive urination, weight loss, microalbuminuria, nephrinuria and display renal histological lesions typical for patients with DN. Patch-clamp electrophysiology performed on podocytes of the freshly isolated glomeruli showed enhanced basal TRPC channel activity in the STZ-SS rats, and increased response to Ang II; total calcium influx triggered by Ang II application was also augmented in podocytes of these rats. Our studies have a strong potential for advancing the understanding of TRPC-mediated effects on podocytopenia in DN initiation.
Author List
Ilatovskaya DV, Levchenko V, Lowing A, Shuyskiy LS, Palygin O, Staruschenko AMESH terms used to index this publication - Major topics in bold
AlbuminuriaAngiotensin II
Animals
Calcium
Diabetic Nephropathies
Disease Models, Animal
Gene Expression
Podocytes
Rats
Rats, Inbred Dahl
TRPC Cation Channels