A novel role for Tm7sf2 gene in regulating TNFα expression.
We have explored the role of Tm7sf2 gene, which codifies for 3β-hydroxysterol Δ14-reductase, an endoplasmic reticulum resident protein, in the sensitivity to endoplasmic reticulum stress and in the resulting inflammatory response. We used mouse embryonic fibroblasts, derived from Tm7sf2(+/+) and Tm7...
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doaj-2e1f03139f4d4796a67bb4a651ef18a72020-11-24T21:56:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6801710.1371/journal.pone.0068017A novel role for Tm7sf2 gene in regulating TNFα expression.Ilaria BellezzaRita RobertiLeonardo GatticchiRachele Del SordoMaria Grazia RambottiMaria Cristina MarchettiAngelo SidoniAlba MinelliWe have explored the role of Tm7sf2 gene, which codifies for 3β-hydroxysterol Δ14-reductase, an endoplasmic reticulum resident protein, in the sensitivity to endoplasmic reticulum stress and in the resulting inflammatory response. We used mouse embryonic fibroblasts, derived from Tm7sf2(+/+) and Tm7sf2(-/-) mice, to determine the in vitro effects of thapsigargin on NF-κB activation. Our results show that the Tm7sf2 gene controls the launch of the unfolded protein response and presides an anti-inflammatory loop thus its absence correlates with NF-κB activation and TNFα up-regulation. Our data also show that Tm7sf2 gene regulates liver X receptor activation and its absence inhibits LXR signalling. By expressing the hTm7sf2 gene in KO MEFs and observing a reduced NF-κB activation, we have confirmed that Tm7sf2 gene is linked to NF-κB activation. Finally we used genetically modified mice in an in vivo model of ER stress and of inflammation. Our results show a significant increase in renal TNFα expression after tunicamycin exposure and in the oedematogenic response in Tm7sf2(-/-) mice. In conclusion, we have shown that the Tm7sf2 gene, to date involved only in cholesterol biosynthesis, also controls an anti-inflammatory loop thereby confirming the existence of cross talk between metabolic pathways and inflammatory response.http://europepmc.org/articles/PMC3720723?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ilaria Bellezza Rita Roberti Leonardo Gatticchi Rachele Del Sordo Maria Grazia Rambotti Maria Cristina Marchetti Angelo Sidoni Alba Minelli |
spellingShingle |
Ilaria Bellezza Rita Roberti Leonardo Gatticchi Rachele Del Sordo Maria Grazia Rambotti Maria Cristina Marchetti Angelo Sidoni Alba Minelli A novel role for Tm7sf2 gene in regulating TNFα expression. PLoS ONE |
author_facet |
Ilaria Bellezza Rita Roberti Leonardo Gatticchi Rachele Del Sordo Maria Grazia Rambotti Maria Cristina Marchetti Angelo Sidoni Alba Minelli |
author_sort |
Ilaria Bellezza |
title |
A novel role for Tm7sf2 gene in regulating TNFα expression. |
title_short |
A novel role for Tm7sf2 gene in regulating TNFα expression. |
title_full |
A novel role for Tm7sf2 gene in regulating TNFα expression. |
title_fullStr |
A novel role for Tm7sf2 gene in regulating TNFα expression. |
title_full_unstemmed |
A novel role for Tm7sf2 gene in regulating TNFα expression. |
title_sort |
novel role for tm7sf2 gene in regulating tnfα expression. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
We have explored the role of Tm7sf2 gene, which codifies for 3β-hydroxysterol Δ14-reductase, an endoplasmic reticulum resident protein, in the sensitivity to endoplasmic reticulum stress and in the resulting inflammatory response. We used mouse embryonic fibroblasts, derived from Tm7sf2(+/+) and Tm7sf2(-/-) mice, to determine the in vitro effects of thapsigargin on NF-κB activation. Our results show that the Tm7sf2 gene controls the launch of the unfolded protein response and presides an anti-inflammatory loop thus its absence correlates with NF-κB activation and TNFα up-regulation. Our data also show that Tm7sf2 gene regulates liver X receptor activation and its absence inhibits LXR signalling. By expressing the hTm7sf2 gene in KO MEFs and observing a reduced NF-κB activation, we have confirmed that Tm7sf2 gene is linked to NF-κB activation. Finally we used genetically modified mice in an in vivo model of ER stress and of inflammation. Our results show a significant increase in renal TNFα expression after tunicamycin exposure and in the oedematogenic response in Tm7sf2(-/-) mice. In conclusion, we have shown that the Tm7sf2 gene, to date involved only in cholesterol biosynthesis, also controls an anti-inflammatory loop thereby confirming the existence of cross talk between metabolic pathways and inflammatory response. |
url |
http://europepmc.org/articles/PMC3720723?pdf=render |
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