TY - JOUR
T1 - Podocyte injury in diabetic nephropathy
T2 - Implications of angiotensin II - dependent activation of TRPC channels
AU - Ilatovskaya, Daria V.
AU - Levchenko, Vladislav
AU - Lowing, Andrea
AU - Shuyskiy, Leonid S.
AU - Palygin, Oleg
AU - Staruschenko, Alexander
N1 - Funding Information:
This research was supported by the NHLBI R01 HL108880, R01 HL122662 (to AS) and T32 HL007852 (to AL), the American Diabetes Association grant 1-15-BS-172 (to AS), the Ben J. Lipps Research Fellowship from the American Society of Nephrology (to DVI), and the Young Investigator Grant from the National Kidney Foundation (to OP). The Authors would like to thank Colleen Lavin (Nikon Inc) for the excellent technical advice and Christine Duris (MCW) for assistance with histological staining.
PY - 2015/12/10
Y1 - 2015/12/10
N2 - 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.
AB - 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.
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U2 - 10.1038/srep17637
DO - 10.1038/srep17637
M3 - Article
C2 - 26656101
AN - SCOPUS:84949591115
SN - 2045-2322
VL - 5
JO - Scientific reports
JF - Scientific reports
M1 - 17637
ER -
