Met provides essential signals for liver regeneration

DOI Web Site 被引用文献34件
  • Malgorzata Borowiak
    Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin-Buch, Germany; and Department of Gastroenterology, Hepatology, and Endocrinology, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany
  • Alistair N. Garratt
    Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin-Buch, Germany; and Department of Gastroenterology, Hepatology, and Endocrinology, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany
  • Torsten Wüstefeld
    Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin-Buch, Germany; and Department of Gastroenterology, Hepatology, and Endocrinology, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany
  • Michael Strehle
    Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin-Buch, Germany; and Department of Gastroenterology, Hepatology, and Endocrinology, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany
  • Christian Trautwein
    Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin-Buch, Germany; and Department of Gastroenterology, Hepatology, and Endocrinology, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany
  • Carmen Birchmeier
    Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin-Buch, Germany; and Department of Gastroenterology, Hepatology, and Endocrinology, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany

抄録

<jats:p>Genetic analysis in mice has demonstrated a crucial role of the Met tyrosine kinase receptor and its ligand, hepatocyte growth factor/scatter factor (HGF/SF), in development of the liver, muscle, and placenta. Here, we use conditional mutagenesis in mice to analyze the function of<jats:italic>Met</jats:italic>during liver regeneration, using the<jats:italic>Mx-cre</jats:italic>transgene to introduce the mutation in the adult. After partial hepatectomy in mice carrying the<jats:italic>Mx-cre</jats:italic>-induced<jats:italic>Met</jats:italic>mutation, regeneration of the liver is impaired. Comparison of signal transduction pathways in control and mutant livers indicates that Met and other signaling receptors cooperate to fully activate particular signaling molecules, for instance, the protein kinase Akt. However, activation of the Erk1/2 kinase during liver regeneration depends exclusively on Met. Signaling crosstalk is thus an important aspect of the regulation of liver regeneration. Analysis of cell cycle progression of hepatocytes in conditional<jats:italic>Met</jats:italic>mutant mice indicates a defective exit from quiescence and diminished entry into S phase. Impaired liver regeneration is accompanied by compensatory physiological responses that include prolonged up-regulation of HGF/SF and IL-6 in peripheral blood. Our data demonstrate that the HGF/SF/Met signaling system is essential not only during liver development but also for the regeneration of the organ in the adult.</jats:p>

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