title: Podocyte injury in diabetic nephropathy: implications of angiotensin II-dependent activation of TRPC channels.
abstract: 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.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: Daria V
authors.initials: DV
authors.lastname: Ilatovskaya
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: Vladislav
authors.initials: V
authors.lastname: Levchenko
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lowing
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.|Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russian Federation.
authors.forename: Leonid S
authors.initials: LS
authors.lastname: Shuyskiy
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: Oleg
authors.initials: O
authors.lastname: Palygin
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.|Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Staruschenko
mesh_terms: D000419:Albuminuria / Q000209:etiology; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D015870:Gene Expression; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D020303:Rats, Inbred Dahl; D050052:TRPC Cation Channels / Q000819:agonists / Q000235:genetics / Q000378:metabolism
chemical_list: D050052:TRPC Cation Channels; C492145:Trpc6 protein, rat; D000804:Angiotensin II; D002118:Calcium