Aging phenotype(s) in kidneys of diabetic mice are p66ShcA dependent.

Aging phenotype(s) in kidneys of diabetic mice are p66ShcA dependent. Am J Physiol Renal Physiol. 2018 Sep 12;: Authors: Vashistha H, Marrero L, Reiss K, Cohen A, Malhotra A, Javed T, Bradley AE, Abbruscato F, Giusti S, Jimenez A, Mehra S, Kaushal D, Giorgio M, Pelicci PG, Kakoki M, Singhal PC, Bunnell B, Meggs LG Abstract The p66ShcA protein controls cellular responses to oxidative stress, senescence and apoptosis. Here, we test the hypothesis that aging phenotype(s) commonly associated with broad category of chronic kidney disease are accelerated in diabetic kidneys and linked to the p66ShcA locus. At the organ level, tissue stem cells antagonize senescent phenotypes, by replacing old dysfunctional cells. Using established methods, we isolated a highly purified population of stem cell antigen-1 positive mesenchymal stem cells (Sca-1+ MSCs) from kidneys of Wild Type (WT) and p66 Knock Out (KO) mice. Cells were plated in culture media containing normal glucose (NG) or high glucose (HG). Reactive oxygen species (ROS) metabolism was substantially increased in Wild Type (WT)-MSCs in HG media in association with increased cell death by apoptosis and acquisition of the senescent phenotype. DNA microarray analysis detected striking differences in the expression profiles of WT and p66 KO-MSCs in HG media. Unexpectedly, the analysis for p66 KO-MSCs revealed upregulation of Wnt genes implicated in self renewal and differentiation. To test the in-vivo consequences...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research

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Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research
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Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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