@PhdThesis{diss_mods_00017531,
  author = 	{M{\"u}ller, Miryam},
  title = 	{The role of a disintegrin and metalloprotease 10 in the liver},
  year = 	{2015},
  publisher = 	{Christian-Albrechts-Universit{\"a}t zu Kiel},
  address = 	{Kiel},
  keywords = 	{ADAM10; Liver; Regeneration; Protease; Progenitor Cells},
  abstract = 	{Proteolytic release of ectodomains at the cell membrane, termed ectodomain shedding, is an irreversible post-translational mechanism to regulate protein function. Members of the a disintegrin and metalloprotease (ADAM) family are key enzymes in shedding of receptors and ligands and, hence, influence cell signaling. Conditional deletion of ADAM10 in murine tissues, such as brain or skin, indicates an essential role for the protease in both organ development and tissue integrity. However, the function of ADAM10 in liver physiology in vivo is largely unknown. We show that in mice with a liver specific deletion of ADAM10 tissue homeostasis in the liver is impaired. Development of the biliary tree, which is dependent on the ADAM10 substrate Notch, was not altered in our mice. Still, mice lacking ADAM10 in the liver developed spontaneous necrosis to various degrees. Interestingly, the liver injury did not cause an increase in pro-inflammatory cytokines. Despite regeneration of the necrotic areas, we observed an accumulation of proliferating liver progenitor cells and a persistent activation of hepatic stellate cells leading to a striking liver fibrosis. We detected, in accordance with these findings, enhanced liver progenitor cell mitogen signaling in a liver progenitor cell line in the absence of ADAM10 activity. Our results demonstrate that ADAM10-mediated proteolytic processing seems to be essential in the termination of liver progenitor cell-driven regenerative processes that, if deregulated, lead to chronic liver disease. They furthermore underline the importance of irreversible post-translational modifications for the maintenance of tissue homeostasis.},
  url = 	{https://macau.uni-kiel.de/receive/diss_mods_00017531},
  file = 	{:https://macau.uni-kiel.de/servlets/MCRFileNodeServlet/dissertation_derivate_00006248/Dissertation_MiryamMueller.pdf:PDF},
  language = 	{en}
}