85. TGF-β Signaling Modulates Hepatocyte Phenotype in Liver Regeneration Following Living Donor Liver Transplant

      Human liver regeneration following partial hepatectomy occurs primarily through normally quiescent hepatocytes that undergo one or two rounds of replication, with restoration of 70% of liver mass after 3-4 months. Liver injury induces a synchronized sequence of events that proceed in an orderly manner with hepatocyte proliferation advancing from the periportal to pericentral areas of the lobule. In contrast, liver repopulation after acute liver failure depends on the differentiation of progenitor cells. Such cells are also present in chronic liver diseases, but their contribution to the production of hepatocytes in those conditions is unknown. We have previously demonstrated small groups of histone positive cells that express stem cell markers Oct3/4, Nanog, Stat3, and CD133 as well as TGF-β members, TGF-β receptor type 2 (TBR2) and ELF, at the end of human liver regeneration at 4 months. Surprisingly, these cells dramatically lose their phenotype to express Oct3/4, Nanog, Stat3, and CD133 but not TGF-β components TBR2 or ELF in hepatocellular cancer (HCC) that often arises in the setting of chronic liver injury. Moreover, genetic disruption of TGF-β signaling in elf+/− mice results in spontaneous HCC that can be reduced by reducing Stat3 signaling (PNAS 2008; 105:2445-2450).
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Surgical Research
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect