The Tm7sf2 Gene Deficiency Protects Mice against Endotoxin-Induced Acute Kidney Injury.
Cholesterol is essential for diverse cellular functions and cellular and whole-body cholesterol homeostasis is highly controlled. Cholesterol can also influence cellular susceptibility to injury. The connection between cholesterol metabolism and inflammation is exemplified by the Tm7sf2 gene, the ab...
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2015-01-01
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doaj-cbf75f0446ef474c93a8bacc6bbcf2d92020-11-25T00:41:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011011e014188510.1371/journal.pone.0141885The Tm7sf2 Gene Deficiency Protects Mice against Endotoxin-Induced Acute Kidney Injury.Leonardo GatticchiIlaria BellezzaRachele Del SordoMatthew J PeirceAngelo SidoniRita RobertiAlba MinelliCholesterol is essential for diverse cellular functions and cellular and whole-body cholesterol homeostasis is highly controlled. Cholesterol can also influence cellular susceptibility to injury. The connection between cholesterol metabolism and inflammation is exemplified by the Tm7sf2 gene, the absence of which reveals an essential role in cholesterol biosynthesis under stress conditions but also results in an inflammatory phenotype, i.e. NF-κB activation and TNFα up-regulation. Here, by using Tm7sf2+/+and Tm7sf2-/- mice, we investigated whether the Tm7sf2 gene, through its role in cholesterol biosynthesis under stress conditions, is involved in the renal failure induced by the administration of LPS. We found that the loss of Tm7sf2 gene results in significantly reduced blood urea nitrogen levels accompanied by decreased renal inflammatory response and neutral lipid accumulation. The increased expression of fatty acids catabolic enzymes reduces the need of the renal autophagy, a known crucial nutrient-sensing pathway in lipid metabolism. Moreover, we observed that the Tm7sf2 insufficiency is responsible for the inhibition of the NF-κB signalling thus dampening the inflammatory response and leading to a reduced renal damage. These results suggest a pivotal role for Tm7sf2 in renal inflammatory and lipotoxic response under endotoxemic conditions.http://europepmc.org/articles/PMC4635018?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Leonardo Gatticchi Ilaria Bellezza Rachele Del Sordo Matthew J Peirce Angelo Sidoni Rita Roberti Alba Minelli |
spellingShingle |
Leonardo Gatticchi Ilaria Bellezza Rachele Del Sordo Matthew J Peirce Angelo Sidoni Rita Roberti Alba Minelli The Tm7sf2 Gene Deficiency Protects Mice against Endotoxin-Induced Acute Kidney Injury. PLoS ONE |
author_facet |
Leonardo Gatticchi Ilaria Bellezza Rachele Del Sordo Matthew J Peirce Angelo Sidoni Rita Roberti Alba Minelli |
author_sort |
Leonardo Gatticchi |
title |
The Tm7sf2 Gene Deficiency Protects Mice against Endotoxin-Induced Acute Kidney Injury. |
title_short |
The Tm7sf2 Gene Deficiency Protects Mice against Endotoxin-Induced Acute Kidney Injury. |
title_full |
The Tm7sf2 Gene Deficiency Protects Mice against Endotoxin-Induced Acute Kidney Injury. |
title_fullStr |
The Tm7sf2 Gene Deficiency Protects Mice against Endotoxin-Induced Acute Kidney Injury. |
title_full_unstemmed |
The Tm7sf2 Gene Deficiency Protects Mice against Endotoxin-Induced Acute Kidney Injury. |
title_sort |
tm7sf2 gene deficiency protects mice against endotoxin-induced acute kidney injury. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2015-01-01 |
description |
Cholesterol is essential for diverse cellular functions and cellular and whole-body cholesterol homeostasis is highly controlled. Cholesterol can also influence cellular susceptibility to injury. The connection between cholesterol metabolism and inflammation is exemplified by the Tm7sf2 gene, the absence of which reveals an essential role in cholesterol biosynthesis under stress conditions but also results in an inflammatory phenotype, i.e. NF-κB activation and TNFα up-regulation. Here, by using Tm7sf2+/+and Tm7sf2-/- mice, we investigated whether the Tm7sf2 gene, through its role in cholesterol biosynthesis under stress conditions, is involved in the renal failure induced by the administration of LPS. We found that the loss of Tm7sf2 gene results in significantly reduced blood urea nitrogen levels accompanied by decreased renal inflammatory response and neutral lipid accumulation. The increased expression of fatty acids catabolic enzymes reduces the need of the renal autophagy, a known crucial nutrient-sensing pathway in lipid metabolism. Moreover, we observed that the Tm7sf2 insufficiency is responsible for the inhibition of the NF-κB signalling thus dampening the inflammatory response and leading to a reduced renal damage. These results suggest a pivotal role for Tm7sf2 in renal inflammatory and lipotoxic response under endotoxemic conditions. |
url |
http://europepmc.org/articles/PMC4635018?pdf=render |
work_keys_str_mv |
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