Proximal Tubule Epithelial Cell Specific Ablation of the Spermidine/spermine N1-acetyltransferase Gene Reduces the Severity of Renal Ischemia/reperfusion Injury

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Nov 13

PMID 25390069

Citations 14

Authors

Kamyar Zahedi

Sharon Barone

Yang Wang

Tracy Murray-Stewart

Prabir Roy-Chaudhury

Roger D Smith

Robert A Casero Jr

Manoocher Soleimani

Affiliations

Soon will be listed here.

Abstract

Background: Expression and activity of spermidine/spermine N1-acetyltransferase (SSAT) increases in kidneys subjected to ischemia/reperfusion (I/R) injury, while its ablation reduces the severity of such injuries. These results suggest that increased SSAT levels contribute to organ injury; however, the role of SSAT specifically expressed in proximal tubule epithelial cells, which are the primary targets of I/R injury, in the mediation of renal damage remains unresolved.

Methods: Severity of I/R injury in wt and renal proximal tubule specific SSAT-ko mice (PT-SSAT-Cko) subjected to bilateral renal I/R injury was assessed using cellular and molecular biological approaches.

Results: Severity of the loss of kidney function and tubular damage are reduced in PT-SSAT-Cko- compared to wt-mice after I/R injury. In addition, animals treated with MDL72527, an inhibitor of polyamine oxidases, had less severe renal damage than their vehicle treated counter-parts. The renal expression of HMGB 1 and Toll like receptors (TLR) 2 and 4 were also reduced in PT-SSAT-Cko- compared to wt mice after I/R injury. Furthermore, infiltration of neutrophils, as well as expression of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) transcripts were lower in the kidneys of PT-SSAT-Cko compared to wt mice after I/R injury. Finally, the activation of caspase3 was more pronounced in the wt compared to PT-SSAT-Cko animals.

Conclusions: Enhanced SSAT expression by proximal tubule epithelial cells leads to tubular damage, and its deficiency reduces the severity of renal I/R injury through reduction of cellular damage and modulation of the innate immune response.

Citing Articles

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Metabolism of Polyamines and Kidney Disease: A Promising Therapeutic Target.

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Zahedi K, Barone S, Soleimani M Med Sci (Basel). 2022; 10(3).

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