CDK inhibitor p21 is prosurvival in adriamycin-induced podocyte injury, in vitro and in vivo.

American Journal of Physiology. Renal Physiology
Caroline B MarshallStuart J Shankland

Abstract

In response to injury, the highly specialized and terminally differentiated glomerular visceral epithelial cell, or podocyte, may undergo several cell fates, including dedifferentiation and proliferation, persistent cell cycle arrest, hypertrophy, apoptosis, or necrosis. Common to these potential outcomes of injury is their ultimate regulation at the level of the cell cycle. There is now a large body of literature confirming the importance of cell cycle regulatory proteins in the cellular response to injury. Although CDK inhibitor p21 levels increase in podocytes following injury, the role of p21 is unclear in focal segmental glomerulosclerosis (FSGS), in part because its function depends heavily on the cytotoxic stimulus and the cellular context. Adriamycin (ADR) is a podocyte toxin used to induce experimental FSGS. The purpose of this study was to define the role of p21 in ADR-induced podocyte injury. BALB/c mice, a strain carrying the recessive ADR susceptibility gene, were backcrossed against c57B6 p21-/- mice to yield a 12th generation BALB/c p21-/- strain. Experimental FSGS was induced by injection of ADR 12 mg/kg × 2 doses (n = 8/group), with mice killed at 1, 2, 8, and 11 wk. Diseased p21-/- mice demonstrated worse albu...Continue Reading

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Citations

Jun 10, 2011·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Dong-Sub JungShin-Wook Kang
Sep 8, 2011·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Alice M ChangStuart J Shankland
Feb 4, 2011·American Journal of Physiology. Renal Physiology·Caroline B MarshallStuart J Shankland
Aug 27, 2011·Journal of the American Society of Nephrology : JASN·Katrien Van BenedenChristiane Van den Branden
Jul 12, 2012·Journal of Applied Toxicology : JAT·Kyu-Bong KimByung-Mu Lee
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Dec 30, 2014·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Dana Thomasova, Hans-Joachim Anders
Sep 7, 2013·The American Journal of Pathology·Helen LiapisHans-Joachim Anders
Jun 24, 2017·Journal of Cellular and Molecular Medicine·Hui TangChun Zhang
Feb 28, 2019·American Journal of Physiology. Renal Physiology·Rohan S BalkawadeCaroline B Marshall
Feb 22, 2017·Aging·Remington R S SchneiderStuart J Shankland
Jan 15, 2015·American Journal of Physiology. Renal Physiology·Guoqing HouCynthia C Tsui

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