期刊
PLOS ONE
卷 8, 期 7, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0068017
关键词
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资金
- PRIN (Progetti di Ricerca di Interesse Nazionele) [20092BE97Y_005]
- Fondazione Cassa di Risparmio di Perugia [2011.0184.021, 2011.0099.021]
We have explored the role of Tm7sf2 gene, which codifies for 3 beta-hydroxysterol Delta 14-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-kappa B 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-kappa B activation and TNF alpha 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-kappa B activation, we have confirmed that Tm7sf2 gene is linked to NF-kappa B 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 TNF alpha 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.
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