Your browser doesn't support javascript.
loading
Interaction of TWEAK with Fn14 leads to the progression of fibrotic liver disease by directly modulating hepatic stellate cell proliferation.
Wilhelm, Annika; Shepherd, Emma L; Amatucci, Aldo; Munir, Mamoona; Reynolds, Gary; Humphreys, Elizabeth; Resheq, Yazid; Adams, David H; Hübscher, Stefan; Burkly, Linda C; Weston, Christopher J; Afford, Simon C.
Afiliación
  • Wilhelm A; Centre for Liver Research and National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit, University of Birmingham, UK.
  • Shepherd EL; Centre for Liver Research and National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit, University of Birmingham, UK.
  • Amatucci A; Department of Immunology, Biogen, Cambridge, MA, USA.
  • Munir M; Centre for Liver Research and National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit, University of Birmingham, UK.
  • Reynolds G; Centre for Liver Research and National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit, University of Birmingham, UK.
  • Humphreys E; Centre for Liver Research and National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit, University of Birmingham, UK.
  • Resheq Y; Centre for Liver Research and National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit, University of Birmingham, UK.
  • Adams DH; Medizinische Klinik 5/Department of Internal Medicine 5, Universitätsklinikum Erlangen/University Medical Centre Erlangen, Germany.
  • Hübscher S; Centre for Liver Research and National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit, University of Birmingham, UK.
  • Burkly LC; Centre for Liver Research and National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Unit, University of Birmingham, UK.
  • Weston CJ; Department of Cellular Pathology, University Hospital Birmingham NHS Foundation Trust, Birmingham, UK.
  • Afford SC; Department of Immunology, Biogen, Cambridge, MA, USA.
J Pathol ; 239(1): 109-21, 2016 May.
Article en En | MEDLINE | ID: mdl-26924336
Tumour necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor-inducible 14 (Fn14) have been associated with liver regeneration in vivo. To further investigate the role of this pathway we examined their expression in human fibrotic liver disease and the effect of pathway deficiency in a murine model of liver fibrosis. The expression of Fn14 and TWEAK in normal and diseased human and mouse liver tissue and primary human hepatic stellate cells (HSCs) were investigated by qPCR, western blotting and immunohistochemistry. In addition, the levels of Fn14 in HSCs following pro-fibrogenic and pro-inflammatory stimuli were assessed and the effects of exogenous TWEAK on HSCs proliferation and activation were studied in vitro. Carbon tetrachloride (CCl4 ) was used to induce acute and chronic liver injury in TWEAK KO mice. Elevated expression of both Fn14 and TWEAK were detected in acute and chronic human liver injury, and co-localized with markers of activated HSCs. Fn14 levels were low in quiescent HSCs but were significantly induced in activated HSCs, which could be further enhanced with the profibrogenic cytokine TGFß in vitro. Stimulation with recombinant TWEAK induced proliferation but not further HSCs activation. Fn14 gene expression was also significantly up-regulated in CCl4 models of hepatic injury whereas TWEAK KO mice showed reduced levels of liver fibrosis following chronic CCl4 injury. In conclusion, TWEAK/Fn14 interaction leads to the progression of fibrotic liver disease via direct modulation of HSCs proliferation, making it a potential therapeutic target for liver fibrosis.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores del Factor de Necrosis Tumoral / Factores de Necrosis Tumoral / Células Estrelladas Hepáticas / Cirrosis Hepática Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: J Pathol Año: 2016 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores del Factor de Necrosis Tumoral / Factores de Necrosis Tumoral / Células Estrelladas Hepáticas / Cirrosis Hepática Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: J Pathol Año: 2016 Tipo del documento: Article Pais de publicación: Reino Unido