The TWEAK/Fn14 Pathway in Tissue Remodeling: For Better or for Worse

Conference paper
First Online:
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 691)

Abstract

Tissues subjected to stress, for example due to mechanical injury, environmental exposures, or endogenous signals, possess a remarkable ability to respond, adapting to limit stress, protect the tissue from further injury, and promote normal tissue recovery. This involves the coordinated activation and regulation of multiple processes, including infiltration by inflammatory cells to remove damaged cells and debris, angiogenesis, extracellular matrix turnover, and progenitor cell expansion and differentiation to regenerate normal tissue. However, in some circumstances inappropriate tissue responses occur, for example acute or prolonged overreactions, wherein the underlying processes are exaggerated and dysregulated, resulting in maladaptive tissue remodeling. A prominent feature of such pathological tissue responses is robust inflammation, as occurs in chronic autoimmune and inflammatory diseases, leading to cell death, progressive damage, and pathological remodeling of the disease target tissue. In the past decade, the ctokine TWEAK and its receptor FN14 have emerged as a ligand/receptor pair of the TNF superfamily that is prominently featured in normal and pathological tissue remodeling. TWEAK/Fn14-induced activities contribute to progressive local tissue damage, maladaptive remodeling, and worsened outcomes in animal models of inflammatory disease.

Keywords

Experimental Autoimmune Encephalomyelitis Human Inflammatory Bowel Disease Fn14 Expression Innate Inflammatory Response Maladaptive Remodel 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

References

  1. 1.
    Burkly LC et al (2007) TWEAKing tissue remodeling by a multifunctional cytokine: role of TWEAK/Fn14 pathway in health and disease. Cytokine 40(1):1–16CrossRefPubMedGoogle Scholar
  2. 2.
    Winkles JA (2008) The TWEAK-Fn14 cytokine-receptor axis: discovery, biology and therapeutic targeting. Nat Rev Drug Discov 7(5):411–425CrossRefPubMedGoogle Scholar
  3. 3.
    Zheng TS, Burkly LC (2008) No end in site: TWEAK/Fn14 activation and autoimmunity associated- end-organ pathologies. J Leukoc Biol 84(2): 338–347CrossRefPubMedGoogle Scholar
  4. 4.
    Dohi T et al (2009) TWEAK/Fn14 pathway: a nonredundant role in intestinal damage in mice through a TWEAK/intestinal epithelial cell axis. Gastroenterology 136(3):912–923CrossRefPubMedGoogle Scholar
  5. 5.
    Chicheportiche Y et al (1997) TWEAK, a new secreted ligand in the tumor necrosis factor family that weakly induces apoptosis. J Biol Chem 272(51):32401–32410CrossRefPubMedGoogle Scholar
  6. 6.
    Felli N et al (2005) Multiple members of the TNF superfamily contribute to IFN-gamma-mediated inhibition of erythropoiesis. J Immunol 175(3):1464–1472PubMedGoogle Scholar
  7. 7.
    Kaplan MJ et al (2002) The apoptotic ligands TRAIL, TWEAK, and Fas ligand mediate monocyte death induced by autologous lupus T cells. J Immunol 169(10):6020–6029PubMedGoogle Scholar
  8. 8.
    Kawakita T et al (2004) Functional expression of TWEAK in human hepatocellular carcinoma: possible implication in cell proliferation and tumor angiogenesis. Biochem Biophys Res Commun 318(3):726–733CrossRefPubMedGoogle Scholar
  9. 9.
    Desplat-Jego S et al (2009) TWEAK is expressed at the cell surface of monocytes during multiple sclerosis. J Leukoc Biol 85(1):132–135CrossRefPubMedGoogle Scholar
  10. 10.
    van Kuijk AW et al (2009) TWEAK and its receptor Fn14 in the synovium of patients with rheumatoid arthritis compared to psoriatic arthritis and its response to TNF blockade. Ann Rheum Dis 69(1):301–304Google Scholar
  11. 11.
    Serafini B et al (2008) Expression of TWEAK and its receptor Fn14 in the multiple sclerosis brain: implications for inflammatory tissue injury. J Neuropathol Exp Neurol 67(12):1137–1148CrossRefPubMedGoogle Scholar
  12. 12.
    Inta I et al (2008) Induction of the cytokine TWEAK and its receptor Fn14 in ischemic stroke. J Neurol Sci 275(1–2):117–120CrossRefPubMedGoogle Scholar
  13. 13.
    Schwartz N et al (2006) Urinary TWEAK and the activity of lupus nephritis. J Autoimmun 27(4):242–250CrossRefPubMedGoogle Scholar
  14. 14.
    Wiley SR et al (2001) A novel TNF receptor family member binds TWEAK and is implicated in angiogenesis. Immunity 15(5):837–846CrossRefPubMedGoogle Scholar
  15. 15.
    Meighan-Mantha RL et al (1999) The mitogen-inducible Fn14 gene encodes a type I transmembrane protein that modulates fibroblast adhesion and migration. J Biol Chem 274(46):33166–33176CrossRefPubMedGoogle Scholar
  16. 16.
    Perper SJ et al (2006) TWEAK is a novel arthritogenic mediator. J Immunol 177(4):2610–2620PubMedGoogle Scholar
  17. 17.
    Zhao Z et al (2007) TWEAK/Fn14 Interactions are instrumental in the pathogenesis of nephritis in the chronic graft-versus-host model of systemic lupus erythematosus. J Immunol 179(11):7949–7958PubMedGoogle Scholar
  18. 18.
    Jakubowski A et al (2002) Dual role for TWEAK in angiogenic regulation. J Cell Sci 115(Pt 2):267–274PubMedGoogle Scholar
  19. 19.
    Chorianopoulos E et al (2009) FGF-inducible 14-kDa protein (Fn14) is regulated via the RhoA/ROCK kinase pathway in cardiomyocytes and mediates nuclear factor-kappaB activation by TWEAK. Basic Res Cardiol 105(2):301–313Google Scholar
  20. 20.
    Munoz-Garcia B et al (2009) Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) enhances vascular and renal damage induced by hyperlipidemic diet in ApoE-knockout mice. Arterioscler Thromb Vasc BiolGoogle Scholar
  21. 21.
    Girgenrath M et al (2006) TWEAK, via its receptor Fn14, is a novel regulator of mesenchymal progenitor cells and skeletal muscle regeneration. Embo J 25(24):5826–5839CrossRefPubMedGoogle Scholar
  22. 22.
    Justo P et al (2006) Cytokine cooperation in renal tubular cell injury: the role of TWEAK. Kidney Int 70(10):1750–1758CrossRefPubMedGoogle Scholar
  23. 23.
    Desplat-Jego S et al (2005) Anti-TWEAK monoclonal antibodies reduce immune cell infiltration in the central nervous system and severity of experimental autoimmune encephalomyelitis. Clin Immunol 117(1):15–23CrossRefPubMedGoogle Scholar
  24. 24.
    Potrovita I et al (2004) Tumor necrosis factor-like weak inducer of apoptosis-induced neurodegeneration. J Neurosci 24(38):8237–8244CrossRefPubMedGoogle Scholar
  25. 25.
    Yepes M et al (2005) A soluble Fn14-Fc decoy receptor reduces infarct volume in a murine model of cerebral ischemia. Am J Pathol 166(2):511–520PubMedGoogle Scholar
  26. 26.
    Jakubowski A et al (2005) TWEAK induces liver progenitor cell proliferation. J Clin Invest 115(9):2330–2340CrossRefPubMedGoogle Scholar
  27. 27.
    Saitoh T et al (2003) TWEAK induces NF-kappaB2 p100 processing and long lasting NF-kappaB activation. J Biol Chem 278(38):36005–36012CrossRefPubMedGoogle Scholar
  28. 28.
    Nakayama M et al (2002) Multiple pathways of TWEAK-induced cell death. J Immunol 168(2):734–743PubMedGoogle Scholar
  29. 29.
    Vince CE et al (2008) TWEAK-FN14 signaling induces lysosomal degradation of a cIAP1-TRAF2 complex to sensitize tumor cells to TNFα. J Cell Biol 182(1):171–184CrossRefPubMedGoogle Scholar
  30. 30.
    Wicovsky A et al (2009) TNF-like weak inducer of apoptosis inhibits proinflammatory TNF receptor-1 signaling. Cell Death Differ 16(11):1445–1459Google Scholar
  31. 31.
    Maecker H et al (2005) TWEAK attenuates the transition from innate to adaptive immunity. Cell 123(5):931–944CrossRefPubMedGoogle Scholar
  32. 32.
    Jain M et al (2009) A novel role for tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in the development of cardiac dysfunction and failure. Circulation 119(15):2058–2068CrossRefPubMedGoogle Scholar
  33. 33.
    Dogra C et al (2007) TNF-related weak inducer of apoptosis (TWEAK) is a potent skeletal muscle-wasting cytokine. FASEB J 21(8):1857–1869CrossRefPubMedGoogle Scholar
  34. 34.
    Desplat-Jego S et al (2002) TWEAK is expressed by glial cells, induces astrocyte proliferation and increases EAE severity. J Neuroimmunol 133(1–2):116–123CrossRefPubMedGoogle Scholar
  35. 35.
    Polavarapu R et al (2005) Tumor necrosis factor-like weak inducer of apoptosis increases the permeability of the neurovascular unit through nuclear factor-kappa B pathway activation. J Neurosci 25(44):10094–10100CrossRefPubMedGoogle Scholar
  36. 36.
    Campbell S et al (2006) Proinflammatory effects of TWEAK/Fn14 interactions in glomerular mesangial cells. J Immunol 176(3):1889–1898PubMedGoogle Scholar
  37. 37.
    Gao HX et al (2009) TNF-like weak inducer of apoptosis (TWEAK) induces inflammatory and proliferative effects in human kidney cells. Cytokine 46(1):24–35CrossRefPubMedGoogle Scholar
  38. 38.
    Sanz AB et al (2008) The cytokine TWEAK modulates renal tubulointerstitial inflammation. J Am Soc Nephrol 19(4):695–703CrossRefPubMedGoogle Scholar
  39. 39.
    Kamata K et al (2006) Involvement of TNF-like weak inducer of apoptosis in the pathogenesis of collagen-induced arthritis. J Immunol 177(9):6433–6439PubMedGoogle Scholar
  40. 40.
    Mueller AM et al (2005) Targeting fibroblast growth factor-inducible-14 signaling protects from chronic relapsing experimental autoimmune encephalomyelitis. J Neuroimmunol 159(1-2):55–65CrossRefPubMedGoogle Scholar
  41. 41.
    Schapira K et al (2009) Fn14-Fc fusion protein regulates atherosclerosis in ApoE–/– mice and inhibits macrophage lipid uptake in vitro. Arterioscler Thromb Vasc Biol 29(12):2021–2027Google Scholar
  42. 42.
    Sanz AB et al (2009) Tweak induces proliferation in renal tubular epithelium: a role in uninephrectomy-induced renal hyperplasia. J Cell Mol Med 13(9B):3329–3342Google Scholar
  43. 43.
    Iocca HA et al (2008) TNF superfamily member TWEAK exacerbates inflammation and demyelination in the cuprizone-induced model. J Neuroimmunol 194(1–2):97–106CrossRefPubMedGoogle Scholar
  44. 44.
    Zhang X et al (2007) TWEAK-Fn14 pathway inhibition protects the integrity of the neurovascular unit during cerebral ischemia. J Cereb Blood Flow Metab 27(3):534–544CrossRefPubMedGoogle Scholar
  45. 45.
    Abreu MT, Fukata M, Arditi M (2005) TLR signaling in the gut in health and disease. J Immunol 174(8):4453–4460PubMedGoogle Scholar
  46. 46.
    Artis D (2008) Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut. Nat Rev Immunol 8(6):411–420CrossRefPubMedGoogle Scholar
  47. 47.
    Gribar SC et al (2008) No longer an innocent bystander: epithelial toll-like receptor signaling in the development of mucosal inflammation. Mol Med 14(9–10):645–659PubMedGoogle Scholar
  48. 48.
    Galamb O et al (2008) Inflammation, adenoma and cancer: objective classification of colon biopsy specimens with gene expression signature. Dis Markers 25(1):1–16PubMedGoogle Scholar
  49. 49.
    Gyorffy B et al (2009) Evaluation of microarray preprocessing algorithms based on concordance with RT-PCR in clinical samples. PLoS One 4(5):e5645CrossRefPubMedGoogle Scholar
  50. 50.
    Kugathasan S et al (2008) Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease. Nat Genet 40(10):1211–1215CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Biogen Idec, Inc.CambridgeUSA
  2. 2.Research Institute, National Center of Global Health and MedicineTokyoJapan

Personalised recommendations