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A disintegrin and metalloprotease 10 (ADAM10) is a central regulator of murine liver tissue homeostasis

A Disintegrin And Metalloprotease (ADAM) 10 exerts essential roles during organ development and tissue integrity in different organs, mainly through activation of the Notch pathway. However, only little is known about its implication in liver tissue physiology. Here we show that in contrast to its r...

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Autores principales: Müller, Miryam, Wetzel, Sebastian, Köhn-Gaone, Julia, Chalupsky, Karel, Lüllmann-Rauch, Renate, Barikbin, Roja, Bergmann, Juri, Wöhner, Birte, Zbodakova, Olga, Leuschner, Ivo, Martin, Gregor, Tiegs, Gisa, Rose-John, Stefan, Sedlacek, Radislav, Tirnitz-Parker, Janina E.E., Saftig, Paul, Schmidt-Arras, Dirk
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951223/
https://www.ncbi.nlm.nih.gov/pubmed/26942887
http://dx.doi.org/10.18632/oncotarget.7836
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author Müller, Miryam
Wetzel, Sebastian
Köhn-Gaone, Julia
Chalupsky, Karel
Lüllmann-Rauch, Renate
Barikbin, Roja
Bergmann, Juri
Wöhner, Birte
Zbodakova, Olga
Leuschner, Ivo
Martin, Gregor
Tiegs, Gisa
Rose-John, Stefan
Sedlacek, Radislav
Tirnitz-Parker, Janina E.E.
Saftig, Paul
Schmidt-Arras, Dirk
author_facet Müller, Miryam
Wetzel, Sebastian
Köhn-Gaone, Julia
Chalupsky, Karel
Lüllmann-Rauch, Renate
Barikbin, Roja
Bergmann, Juri
Wöhner, Birte
Zbodakova, Olga
Leuschner, Ivo
Martin, Gregor
Tiegs, Gisa
Rose-John, Stefan
Sedlacek, Radislav
Tirnitz-Parker, Janina E.E.
Saftig, Paul
Schmidt-Arras, Dirk
author_sort Müller, Miryam
collection PubMed
description A Disintegrin And Metalloprotease (ADAM) 10 exerts essential roles during organ development and tissue integrity in different organs, mainly through activation of the Notch pathway. However, only little is known about its implication in liver tissue physiology. Here we show that in contrast to its role in other tissues, ADAM10 is dispensable for the Notch2-dependent biliary tree formation. However, we demonstrate that expression of bile acid transporters is dependent on ADAM10. Consequently, mice deficient for Adam10 in hepatocytes, cholangiocytes and liver progenitor cells develop spontaneous hepatocyte necrosis and concomitant liver fibrosis. We furthermore observed a strongly augmented ductular reaction in 15-week old ADAM10(Δhep/Δch) mice and demonstrate that c-Met dependent liver progenitor cell activation is enhanced. Additionally, liver progenitor cells are primed to hepatocyte differentiation in the absence of ADAM10. These findings show that ADAM10 is a novel central node controlling liver tissue homeostasis. Highlights: Loss of ADAM10 in murine liver results in hepatocyte necrosis and concomitant liver fibrosis. ADAM10 directly regulates expression of bile acid transporters but is dispensable for Notch2-dependent formation of the biliary system. Activation of liver progenitor cells is enhanced through increased c-Met signalling, in the absence of ADAM10. Differentiation of liver progenitor cells to hepatocytes is augmented in the absence of ADAM10.
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spelling pubmed-49512232016-07-21 A disintegrin and metalloprotease 10 (ADAM10) is a central regulator of murine liver tissue homeostasis Müller, Miryam Wetzel, Sebastian Köhn-Gaone, Julia Chalupsky, Karel Lüllmann-Rauch, Renate Barikbin, Roja Bergmann, Juri Wöhner, Birte Zbodakova, Olga Leuschner, Ivo Martin, Gregor Tiegs, Gisa Rose-John, Stefan Sedlacek, Radislav Tirnitz-Parker, Janina E.E. Saftig, Paul Schmidt-Arras, Dirk Oncotarget Research Paper: Pathology A Disintegrin And Metalloprotease (ADAM) 10 exerts essential roles during organ development and tissue integrity in different organs, mainly through activation of the Notch pathway. However, only little is known about its implication in liver tissue physiology. Here we show that in contrast to its role in other tissues, ADAM10 is dispensable for the Notch2-dependent biliary tree formation. However, we demonstrate that expression of bile acid transporters is dependent on ADAM10. Consequently, mice deficient for Adam10 in hepatocytes, cholangiocytes and liver progenitor cells develop spontaneous hepatocyte necrosis and concomitant liver fibrosis. We furthermore observed a strongly augmented ductular reaction in 15-week old ADAM10(Δhep/Δch) mice and demonstrate that c-Met dependent liver progenitor cell activation is enhanced. Additionally, liver progenitor cells are primed to hepatocyte differentiation in the absence of ADAM10. These findings show that ADAM10 is a novel central node controlling liver tissue homeostasis. Highlights: Loss of ADAM10 in murine liver results in hepatocyte necrosis and concomitant liver fibrosis. ADAM10 directly regulates expression of bile acid transporters but is dispensable for Notch2-dependent formation of the biliary system. Activation of liver progenitor cells is enhanced through increased c-Met signalling, in the absence of ADAM10. Differentiation of liver progenitor cells to hepatocytes is augmented in the absence of ADAM10. Impact Journals LLC 2016-03-01 /pmc/articles/PMC4951223/ /pubmed/26942887 http://dx.doi.org/10.18632/oncotarget.7836 Text en Copyright: © 2016 Müller et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper: Pathology
Müller, Miryam
Wetzel, Sebastian
Köhn-Gaone, Julia
Chalupsky, Karel
Lüllmann-Rauch, Renate
Barikbin, Roja
Bergmann, Juri
Wöhner, Birte
Zbodakova, Olga
Leuschner, Ivo
Martin, Gregor
Tiegs, Gisa
Rose-John, Stefan
Sedlacek, Radislav
Tirnitz-Parker, Janina E.E.
Saftig, Paul
Schmidt-Arras, Dirk
A disintegrin and metalloprotease 10 (ADAM10) is a central regulator of murine liver tissue homeostasis
title A disintegrin and metalloprotease 10 (ADAM10) is a central regulator of murine liver tissue homeostasis
title_full A disintegrin and metalloprotease 10 (ADAM10) is a central regulator of murine liver tissue homeostasis
title_fullStr A disintegrin and metalloprotease 10 (ADAM10) is a central regulator of murine liver tissue homeostasis
title_full_unstemmed A disintegrin and metalloprotease 10 (ADAM10) is a central regulator of murine liver tissue homeostasis
title_short A disintegrin and metalloprotease 10 (ADAM10) is a central regulator of murine liver tissue homeostasis
title_sort disintegrin and metalloprotease 10 (adam10) is a central regulator of murine liver tissue homeostasis
topic Research Paper: Pathology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4951223/
https://www.ncbi.nlm.nih.gov/pubmed/26942887
http://dx.doi.org/10.18632/oncotarget.7836
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