Nephrology Commons^™

Fluid Flow Shear Stress Over Podocytes Is Increased In The Solitary Kidney., Tarak Srivastava, Gianni E. Celsi, Mukut Sharma, Hongying Dai, Ellen T. Mccarthy, Melanie Ruiz, Patricia A. Cudmore, Uri S. Alon, Ram Sharma, Virginia A. Savin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Glomerular hyperfiltration is emerging as the key risk factor for progression of chronic kidney disease (CKD). Podocytes are exposed to fluid flow shear stress (FFSS) caused by the flow of ultrafiltrate within Bowman's space. The mechanism of hyperfiltration-induced podocyte injury is not clear. We postulated that glomerular hyperfiltration in solitary kidney increases FFSS over podocytes.

METHODS: Infant Sprague-Dawley rats at 5 days of age and C57BL/6J 14-week-old adult mice underwent unilateral nephrectomy. Micropuncture and morphological studies were then performed on 20- and 60-day-old rats. FFSS over podocytes in uninephrectomized rats and mice was calculated using the recently published equation …

Endoplasmic Reticulum Calcium-Independent Phospholipase A2 Gamma (Er-Ipla2Γ): Role In Oxidative Stress-Induced Lipid Peroxidation, Ca2+ Release, Phospholipid Homeostasis And Cell Death In The Kidney, Andre Chioke Eaddy

MUSC Theses and Dissertations

Acute kidney injury and chronic kidney disease are becoming more prevalent and have high morbidity and mortality, and despite several therapies targeted towards treating or preventing kidney injury, outcomes have been unchanged for many years. Calcium­independent phospholipase A2y (iPLA2γ) is one of seven Ca2+-independent PLA2 enzymes and represents a potential therapeutic target in kidney disease because of its unique subcellular localization and its potential as the putative membrane remodeling/repair enzyme. Studies in our laboratory suggest iPLA2γ is cytoprotective during oxidant injury by preventing and/or repairing oxidant-induced lipid peroxidation and pointed to ER-iPLA2γ as the major component of membrane repair and …

Rho Activation Of Mdia Formins Is Modulated By An Interaction With Inverted Formin 2 (Inf2), Hua Sun, Johannes S. Schlondorff, Elizabeth J. Brown, Henry N. Higgs, Martin R. Pollak

Dartmouth Scholarship

Inverted formin 2 (INF2) encodes a member of the diaphanous subfamily of formin proteins. Mutations in INF2 cause human kidney disease characterized by focal and segmental glomerulosclerosis. Disease-causing mutations occur only in the diaphanous inhibitory domain (DID), suggesting specific roles for this domain in the pathogenesis of disease. In a yeast two-hybrid screen, we identified the diaphanous autoregulatory domains (DADs) of the mammalian diaphanous-related formins (mDias) mDia1, mDia2, and mDia 3 as INF2_DID-interacting partners. The mDias are Rho family effectors that regulate actin dynamics. We confirmed in vitro INF2_DID/mDia_DAD binding by biochemical assays, confirmed the in vivo interaction of these …

Multiple Metabolic Hits Converge On Cd36 As Novel Mediator Of Tubular Epithelial Apoptosis In Diabetic Nephropathy., Katalin Susztak, Emilio Ciccone, Peter Mccue, Kumar Sharma, Erwin P Böttinger

Department of Medicine Faculty Papers

BACKGROUND: Diabetic nephropathy (DNP) is a common complication of type 1 and type 2 diabetes mellitus and the most common cause of kidney failure. While DNP manifests with albuminuria and diabetic glomerulopathy, its progression correlates best with tubular epithelial degeneration (TED) and interstitial fibrosis. However, mechanisms leading to TED in DNP remain poorly understood.

METHODS AND FINDINGS: We found that expression of scavenger receptor CD36 coincided with proximal tubular epithelial cell (PTEC) apoptosis and TED specifically in human DNP. High glucose stimulated cell surface expression of CD36 in PTECs. CD36 expression was necessary and sufficient to mediate PTEC apoptosis induced …