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HNF‐Regulated Epithelial Differentiation in Human Liver Diseases
Author(s) -
Ochoa Erin Rubin,
Alarcon Gabriela,
Demetris Anthony J.,
Nalesnik Michael A.,
Walls Andrew,
Michalopoulos George K.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a72-a
Subject(s) - hepatocyte , biology , pathology , transdifferentiation , medicine , microbiology and biotechnology , stem cell , biochemistry , in vitro
Hepatocyte nuclear factors or HNF regulate the differentiation of hepatocytes and biliary epithelial cells (BEC) from embryonic hepatoblasts. In massive hepatic necrosis (MHN) and in partial hepatectomy models, progeny of BEC in Canals of Herring transform into hepatocytes. Converse transformation of hepatocytes into BEC has been seen in PH rats treated with biliary toxin DAPM and bile duct ligation. We investigated whether alterations in HNF expression in the adult human diseased liver correlate to ductal plate remodeling during hepatogenesis. Immunohistochemical analysis of HNF‐1α/β, 3α/β,4,6, HepPar1 and CK19 were performed on paraffin embedded human specimens from 5 cases each of 1–3 rd trimester fetal, adult normal (NL) and diseased livers (biliary obstruction (BO), Budd‐Chiari syndrome (BCS), MHN, HCV, and PBC). HNF‐4α and ‐6 were expressed exclusively in NL hepatocytes and upregulated in BEC and HepPar1+/CK19+ ductules in MHN, HCV and BCS. HNF‐3β, expressed in NL BEC, was expressed in hepatocytes in PBC, BO and BCS. Our data shows that HNF expression correlates to hepatobiliary transdifferentiation in disease states. It may be that depending upon the type of epithelial injury in the liver, HNF expression varies to either drive the production of hepatocytes or biliary epithelial cells. Careful sequential characterization studies may provide important insights into hepatic repair responses.