Invited Review- The Endoplasmic Reticulum Stress Response and Diabetic Kidney
Disease.
Authors Cunard R, Sharma K
Submitted By Kumar Sharma on 5/2/2011
Status Published
Journal American journal of physiology. Renal physiology
Year 2011
Date Published 5/1/2011
Volume : Pages Not Specified : Not Specified
PubMed Reference 21345978
Abstract The Endoplasmic Reticulum (ER) folds and modifies proteins, however during
conditions of cellular stress, unfolded proteins accumulate in the ER and
activate the Unfolded Protein Response (UPR). The UPR also referred to as the ER
Stress Response activates three distinct signaling cascades that are designed to
globally reduce transcription and translation. The three major arms of the
mammalian UPR include: 1) protein kinase RNA (PKR)-like ER kinase (PERK) 2)
inositol requiring protein-1 (IRE1a) and 3) activating transcription factor-6
(ATF6) pathways. The PERK pathway rapidly attenuates protein translation,
whereas the ATF6 and the IRE1a cascades transcriptionally upregulate ER
chaperone genes that promote proper folding and ER-associated degradation (ERAD)
of proteins. This integrated response in turn allows the folding machinery of
the ER to catch up with the backlog of unfolded proteins. The ER stress response
plays a role in a number of patho-physiologic processes, including pancreatic
ß-cell failure and apoptosis. The goals of the current review are to familiarize
investigators with cellular and tissue activation of this response in the rodent
and human diabetic kidney. Additionally we will review therapeutic modulators of
the ER Stress response and discuss their efficacy in models of diabetic kidney
disease. The ER Stress response has both protective and deleterious features. A
better understanding of the molecular pathways regulated during this process in
a cell and disease-specific manner could reveal novel therapeutic strategies in
chronic renal diseases, including diabetic kidney disease.


Investigators with authorship
NameInstitution
Kumar SharmaUniversity of California San Diego

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