A novel role for Tm7sf2 gene in regulating TNF? expression.

ABSTRACT: We have explored the role of Tm7sf2 gene, which codifies for 3?-hydroxysterol ?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-?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-?B activation and TNF? 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-?B activation, we have confirmed that Tm7sf2 gene is linked to NF-?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? 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.

SUBMITTER: Bellezza I 

PROVIDER: S-EPMC3720723 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature