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

  • Linda C. Burkly
  • Taeko Dohi
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 691)


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.


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.


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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

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