| First Author | Bellezza I | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 7 | Pages | e68017 |
| PubMed ID | 23935851 | Mgi Jnum | J:204692 |
| Mgi Id | MGI:5538442 | Doi | 10.1371/journal.pone.0068017 |
| Citation | Bellezza I, et al. (2013) A novel role for Tm7sf2 gene in regulating TNFalpha expression. PLoS One 8(7):e68017 |
| abstractText | We have explored the role of Tm7sf2 gene, which codifies for 3beta-hydroxysterol Delta14-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-kappaB 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-kappaB activation and TNFalpha 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-kappaB activation, we have confirmed that Tm7sf2 gene is linked to NF-kappaB 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 TNFalpha 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. |
