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Tnfsf12  -  tumor necrosis factor (ligand) superfamily...

Mus musculus

Synonyms: APO3L, Apo3l, DR3L, Dr3l, Dr3lg, ...
 
 
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Disease relevance of Tnfsf12

  • Several of the TWEAK-inducible cytokines are important in the pathogenesis of kidney diseases; however, whether TWEAK can induce a proinflammatory effect on kidney cells is not known [1].
  • TWEAK-/- mice had overabundant natural killer (NK) cells and displayed hypersensitivity to bacterial endotoxin, with their innate immune cells producing excess interferon (IFN)-gamma and interleukin (IL)-12 [2].
  • Transgenic mice overexpressing TWEAK in hepatocytes exhibit periportal oval cell hyperplasia [3].
  • A similar phenotype was obtained in adult wild-type mice, but not Fn14-null mice, by administering TWEAK-expressing adenovirus [3].
  • Finally, we show increased Fn14 expression in chronic hepatitis C and other human liver diseases relative to its expression in normal liver, which suggests a role for the TWEAK/Fn14 pathway in human liver injury [3].
  • Mice with induced Lupus treated with an anti-TWEAK neutralizing mAb had significantly diminished kidney expression of IL-6, MCP-1, IL-10, as well as proteinuria, but similar autoantibody titers, as compared with control-treated mice [4].
 

High impact information on Tnfsf12

 

Chemical compound and disease context of Tnfsf12

  • After 24 hr of focal cerebral ischemia in vivo or oxygen glucose deprivation in primary cortical neurons, both TWEAK and its receptor Fn14 were significantly upregulated [6].
  • These results demonstrated that TWEAK mRNA, contrary to TNF mRNA, is stable, ubiquitously distributed in tissues, and is down-regulated after LPS treatment or in chronic inflammation, suggesting that TWEAK could be an important factor, along with TNF, in acute and chronic inflammations [7].
 

Biological context of Tnfsf12

 

Anatomical context of Tnfsf12

  • Recently, fibroblast growth factor-inducible 14 (Fn14) was suggested to be a receptor for TWEAK [11].
  • We conclude that TWEAK induces mesangial cells to secrete proinflammatory chemokines, suggesting a prominent role for TWEAK in the pathogenesis of renal injury [1].
  • Ligation of the TWEAK receptor Fn14 by TWEAK has proinflammatory effects on fibroblasts, synoviocytes, and endothelial cells [1].
  • We describe our findings showing that TWEAK mediated the differentiation of RAW264.7 (RAW) monocyte/macrophage cells into multinuclear, functional osteoclasts [11].
  • Moreover, anti-TWEAK mAb treatment promoted the subcutaneous growth of TWEAK-sensitive Fn14-expressing tumor cells, and this promotion was abolished by the inhibition of macrophage infiltration but not NK cell depletion [12].
 

Associations of Tnfsf12 with chemical compounds

 

Regulatory relationships of Tnfsf12

  • Finally, TWEAK-induced chemokine secretion was prevented by treatment with novel murine anti-TWEAK Abs [1].
  • We found that intracerebral injection of TWEAK in wild-type mice induces activation of the nuclear factor-kappaB (NF-kappaB) pathway and matrix metalloproteinase-9 (MMP-9) expression in the brain with resultant disruption in the structure of the NVU and increase in the permeability of the blood-brain barrier (BBB) [16].
 

Other interactions of Tnfsf12

 

Analytical, diagnostic and therapeutic context of Tnfsf12

References

  1. Proinflammatory effects of TWEAK/Fn14 interactions in glomerular mesangial cells. Campbell, S., Burkly, L.C., Gao, H.X., Berman, J.W., Su, L., Browning, B., Zheng, T., Schiffer, L., Michaelson, J.S., Putterman, C. J. Immunol. (2006) [Pubmed]
  2. TWEAK attenuates the transition from innate to adaptive immunity. Maecker, H., Varfolomeev, E., Kischkel, F., Lawrence, D., LeBlanc, H., Lee, W., Hurst, S., Danilenko, D., Li, J., Filvaroff, E., Yang, B., Daniel, D., Ashkenazi, A. Cell (2005) [Pubmed]
  3. TWEAK induces liver progenitor cell proliferation. Jakubowski, A., Ambrose, C., Parr, M., Lincecum, J.M., Wang, M.Z., Zheng, T.S., Browning, B., Michaelson, J.S., Baetscher, M., Baestcher, M., Wang, B., Bissell, D.M., Burkly, L.C. J. Clin. Invest. (2005) [Pubmed]
  4. TWEAK/Fn14 interactions are instrumental in the pathogenesis of nephritis in the chronic graft-versus-host model of systemic lupus erythematosus. Zhao, Z., Burkly, L.C., Campbell, S., Schwartz, N., Molano, A., Choudhury, A., Eisenberg, R.A., Michaelson, J.S., Putterman, C. J. Immunol. (2007) [Pubmed]
  5. TWEAK, via its receptor Fn14, is a novel regulator of mesenchymal progenitor cells and skeletal muscle regeneration. Girgenrath, M., Weng, S., Kostek, C.A., Browning, B., Wang, M., Brown, S.A., Winkles, J.A., Michaelson, J.S., Allaire, N., Schneider, P., Scott, M.L., Hsu, Y.M., Yagita, H., Flavell, R.A., Miller, J.B., Burkly, L.C., Zheng, T.S. EMBO J. (2006) [Pubmed]
  6. Tumor necrosis factor-like weak inducer of apoptosis-induced neurodegeneration. Potrovita, I., Zhang, W., Burkly, L., Hahm, K., Lincecum, J., Wang, M.Z., Maurer, M.H., Rossner, M., Schneider, A., Schwaninger, M. J. Neurosci. (2004) [Pubmed]
  7. Down-regulated expression of TWEAK mRNA in acute and chronic inflammatory pathologies. Chicheportiche, Y., Fossati-Jimack, L., Moll, S., Ibnou-Zekri, N., Izui, S. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  8. A soluble Fn14-Fc decoy receptor reduces infarct volume in a murine model of cerebral ischemia. Yepes, M., Brown, S.A., Moore, E.G., Smith, E.P., Lawrence, D.A., Winkles, J.A. Am. J. Pathol. (2005) [Pubmed]
  9. TWEAK is a novel arthritogenic mediator. Perper, S.J., Browning, B., Burkly, L.C., Weng, S., Gao, C., Giza, K., Su, L., Tarilonte, L., Crowell, T., Rajman, L., Runkel, L., Scott, M., Atkins, G.J., Findlay, D.M., Zheng, T.S., Hess, H. J. Immunol. (2006) [Pubmed]
  10. The Fn14 cytoplasmic tail binds tumour-necrosis-factor-receptor-associated factors 1, 2, 3 and 5 and mediates nuclear factor-kappaB activation. Brown, S.A., Richards, C.M., Hanscom, H.N., Feng, S.L., Winkles, J.A. Biochem. J. (2003) [Pubmed]
  11. TWEAK mediates signal transduction and differentiation of RAW264.7 cells in the absence of Fn14/TweakR. Evidence for a second TWEAK receptor. Polek, T.C., Talpaz, M., Darnay, B.G., Spivak-Kroizman, T. J. Biol. Chem. (2003) [Pubmed]
  12. TWEAK mediates anti-tumor effect of tumor-infiltrating macrophage. Kaduka, Y., Takeda, K., Nakayama, M., Kinoshita, K., Yagita, H., Okumura, K. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  13. Intraovarian tumor necrosis factor-related weak inducer of apoptosis/fibroblast growth factor-inducible-14 ligand-receptor system limits ovarian preovulatory follicles from excessive luteinization. De, A., Park, J.I., Kawamura, K., Chen, R., Klein, C., Rauch, R., Mulders, S.M., Sollewijn Gelpke, M.D., Hsueh, A.J. Mol. Endocrinol. (2006) [Pubmed]
  14. Characterization of murine TWEAK and its receptor (Fn14) by monoclonal antibodies. Nakayama, M., Harada, N., Okumura, K., Yagita, H. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  15. Tumor necrosis factor-like weak inducer of apoptosis inhibits skeletal myogenesis through sustained activation of nuclear factor-kappaB and degradation of MyoD protein. Dogra, C., Changotra, H., Mohan, S., Kumar, A. J. Biol. Chem. (2006) [Pubmed]
  16. Tumor necrosis factor-like weak inducer of apoptosis increases the permeability of the neurovascular unit through nuclear factor-kappa B pathway activation. Polavarapu, R., Gongora, M.C., Winkles, J.A., Yepes, M. J. Neurosci. (2005) [Pubmed]
  17. TWEAK induces NF-kappaB2 p100 processing and long lasting NF-kappaB activation. Saitoh, T., Nakayama, M., Nakano, H., Yagita, H., Yamamoto, N., Yamaoka, S. J. Biol. Chem. (2003) [Pubmed]
  18. NF-kappaB signalling in cerebral ischaemia. Schwaninger, M., Inta, I., Herrmann, O. Biochem. Soc. Trans. (2006) [Pubmed]
  19. Targeting fibroblast growth factor-inducible-14 signaling protects from chronic relapsing experimental autoimmune encephalomyelitis. Mueller, A.M., Pedré, X., Kleiter, I., Hornberg, M., Steinbrecher, A., Giegerich, G. J. Neuroimmunol. (2005) [Pubmed]
 
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