Cellular and Molecular Cascades during Liver Regeneration

The demand for organs such as the liver for patients with end stage disease is greater than what is currently available. Thus, there is a dire need to have alternative solutions, for which none exist at the moment. Investigating the key underlying mechanisms involved not only in liver regeneration and repair, but also in development, can give us a better under- standing of how to promote a pro-regenerative phenotype in the liver. This review will focus on the cellular and molecular aspects of liver regeneration and address signaling mechanisms involved in liver development and how they are recapitulated in regeneration after a partial hepatectomy.

[1]  E. Pikarsky,et al.  Adult hepatocytes are generated by self-duplication rather than stem cell differentiation. , 2014, Cell stem cell.

[2]  Cassandra R Diegel,et al.  Beta‐catenin signaling in murine liver zonation and regeneration: A Wnt‐Wnt situation! , 2014, Hepatology.

[3]  B. Alman,et al.  β-Catenin-regulated myeloid cell adhesion and migration determine wound healing. , 2014, The Journal of clinical investigation.

[4]  A. Miyajima,et al.  Stem/progenitor cells in liver development, homeostasis, regeneration, and reprogramming. , 2014, Cell stem cell.

[5]  Susanne Bartels,et al.  Endothelial Cell-Derived Angiopoietin-2 Controls Liver Regeneration as a Spatiotemporal Rheostat , 2014, Science.

[6]  Michael Simons,et al.  Divergent angiocrine signals from vascular niche balance liver regeneration and fibrosis , 2013, Nature.

[7]  N. Rosenthal,et al.  Macrophages are required for adult salamander limb regeneration , 2013, Proceedings of the National Academy of Sciences.

[8]  D. Häussinger,et al.  Hepatic stem cell niches. , 2013, The Journal of clinical investigation.

[9]  D. Stainier,et al.  Hepatic stellate cells in liver development, regeneration, and cancer. , 2013, The Journal of clinical investigation.

[10]  Satoko Arakawa,et al.  Hypertrophy and Unconventional Cell Division of Hepatocytes Underlie Liver Regeneration , 2012, Current Biology.

[11]  M. Manns,et al.  Angiopoietin-2 in acute liver failure* , 2012, Critical care medicine.

[12]  T. Roskams,et al.  Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease , 2012, Nature Medicine.

[13]  E. Ober,et al.  Interplay between Wnt2 and Wnt2bb controls multiple steps of early foregut-derived organ development , 2011, Development.

[14]  Percy A. Knolle,et al.  Antigen-presenting cell function in the tolerogenic liver environment , 2010, Nature Reviews Immunology.

[15]  Zev Rosenwaks,et al.  Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration , 2010, Nature.

[16]  G. Karaca,et al.  Hedgehog signaling is critical for normal liver regeneration after partial hepatectomy in mice , 2010, Hepatology.

[17]  B. Petersen,et al.  Hepatic stellate cells’ involvement in progenitor mediated liver regeneration , 2010, Laboratory Investigation.

[18]  Z. Granot,et al.  Pregnancy restores the regenerative capacity of the aged liver via activation of an mTORC1-controlled hyperplasia/hypertrophy switch. , 2010, Genes & development.

[19]  Steven A Curley,et al.  Three Hundred and One Consecutive Extended Right Hepatectomies: Evaluation of Outcome Based on Systematic Liver Volumetry , 2009, Annals of surgery.

[20]  A. Miyajima,et al.  Hedgehog signal activation coordinates proliferation and differentiation of fetal liver progenitor cells. , 2009, Experimental cell research.

[21]  D. Sargent,et al.  Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  B. Stanger,et al.  Notch signaling controls liver development by regulating biliary differentiation , 2009, Development.

[23]  M. Jeschke.  The Hepatic Response to Thermal Injury: Is the Liver Important for Postburn Outcomes? , 2009, Molecular medicine.

[24]  P. Li,et al.  Mesenchymal origin of hepatic stellate cells, submesothelial cells, and perivascular mesenchymal cells during mouse liver development , 2009, Hepatology.

[25]  S. Islam,et al.  Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly , 2009, The Journal of pathology.

[26]  S. Lowe,et al.  Senescence of Activated Stellate Cells Limits Liver Fibrosis , 2008, Cell.

[27]  P. Mazur,et al.  Liver‐specific inactivation of Notch2, but not Notch1, compromises intrahepatic bile duct development in mice , 2008, Hepatology.

[28]  G. Alpini,et al.  Fate‐Mapping Evidence That Hepatic Stellate Cells Are Epithelial Progenitors in Adult Mouse Livers , 2008, Stem cells.

[29]  Ken Matsumoto,et al.  Wnt9a secreted from the walls of hepatic sinusoids is essential for morphogenesis, proliferation, and glycogen accumulation of chick hepatic epithelium. , 2008, Developmental biology.

[30]  S. Monga,et al.  Wnt/β-catenin signaling in hepatic organogenesis , 2008 .

[31]  A. Zorn,et al.  Repression of Wnt/β-catenin signaling in the anterior endoderm is essential for liver and pancreas development , 2007, Development.

[32]  D. Stainier,et al.  Bmp and Fgf signaling are essential for liver specification in zebrafish , 2007, Development.

[33]  H. Petrowsky,et al.  Strategies for safer liver surgery and partial liver transplantation. , 2007, The New England journal of medicine.

[34]  D. Häussinger,et al.  CD133+ hepatic stellate cells are progenitor cells. , 2007, Biochemical and biophysical research communications.

[35]  E. Abdalla,et al.  Improving Resectability of Hepatic Colorectal Metastases: Expert Consensus Statement , 2006, Annals of Surgical Oncology.

[36]  M. Ychou,et al.  Towards a pan-European consensus on the treatment of patients with colorectal liver metastases. , 2006, European journal of cancer.

[37]  D. Stainier,et al.  Mesodermal Wnt2b signalling positively regulates liver specification , 2006, Nature.

[38]  D. Moore,et al.  Nuclear Receptor-Dependent Bile Acid Signaling Is Required for Normal Liver Regeneration , 2006, Science.

[39]  O. Garden,et al.  Surgical resection of hepatic metastases from colorectal cancer: A systematic review of published studies , 2006, British Journal of Cancer.

[40]  K. Zaret,et al.  Distinct populations of endoderm cells converge to generate the embryonic liver bud and ventral foregut tissues. , 2005, Developmental biology.

[41]  R. Taub.  Liver regeneration: from myth to mechanism , 2004, Nature Reviews Molecular Cell Biology.

[42]  A. Miyajima,et al.  Notch signaling controls hepatoblast differentiation by altering the expression of liver-enriched transcription factors , 2004, Journal of Cell Science.

[43]  F. Lemaigre.  Development of the biliary tract , 2003, Mechanisms of Development.

[44]  Yan Zhou,et al.  Foxf1 +/− mice exhibit defective stellate cell activation and abnormal liver regeneration following CCl4 injury , 2003, Hepatology.

[45]  A. Su,et al.  Gene expression during the priming phase of liver regeneration after partial hepatectomy in mice , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[46]  E. Sandgren,et al.  Timing of hepatocyte entry into DNA synthesis after partial hepatectomy is cell autonomous. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[47]  H. Schouten,et al.  Kupffer cell depletion by CI2MDP-liposomes alters hepatic cytokine expression and delays liver regeneration after partial hepatectomy. , 2000, Liver.

[48]  K. Zaret,et al.  Initiation of mammalian liver development from endoderm by fibroblast growth factors. , 1999, Science.

[49]  Colin C. Collins,et al.  Alagille syndrome is caused by mutations in human Jagged1, which encodes a ligand for Notch1 , 1997, Nature Genetics.

[50]  S. Glaser,et al.  Regrowth of the rat biliary tree after 70% partial hepatectomy is coupled to increased secretin-induced ductal secretion. , 1996, Gastroenterology.

[51]  E. Medlock,et al.  The liver hemopoietic environment: II. Peroxidase reactive mouse fetal liver hemopoietic cells , 1983, The Anatomical record.

[52]  E. Houssaint.  Differentiation of the mouse hepatic primordium. I. An analysis of tissue interactions in hepatocyte differentiation. , 1980, Cell differentiation.

[53]  G. Michalopoulos.  Liver regeneration after partial hepatectomy: critical analysis of mechanistic dilemmas. , 2010, The American journal of pathology.

[54]  H. Willenbring,et al.  A reproducible and well-tolerated method for 2/3 partial hepatectomy in mice , 2008, Nature Protocols.

[55]  Robert Opoka,et al.  FGF signaling is necessary for establishing gut tube domains alongthe anterior–posterior axis in vivo , 2006, Mechanisms of Development.

[56]  G. Michalopoulos,et al.  Beta-catenin antisense studies in embryonic liver cultures: role in proliferation, apoptosis, and lineage specification. , 2003, Gastroenterology.

[57]  G. Michalopoulos,et al.  Liver Regeneration , 1997, Science.