PMID- 8601590
OWN - NLM
STAT- MEDLINE
DCOM- 19960509
LR  - 20190508
IS  - 0021-9525 (Print)
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Linking)
VI  - 132
IP  - 6
DP  - 1996 Mar
TI  - Population expansion, clonal growth, and specific differentiation patterns in 
      primary cultures of hepatocytes induced by HGF/SF, EGF and TGF alpha in a 
      chemically defined (HGM) medium.
PG  - 1133-49
AB  - Mature adult parenchymal hepatocytes, typically of restricted capacity to 
      proliferate in culture, can now enter into clonal growth under the influence of 
      hepatocyte growth factor (scatter factor) (HGF/SF), epidermal growth factor 
      (EGF), and transforming growth factor alpha (TGFalpha) in the presence of a new 
      chemically defined medium (HGM). The expanding populations of hepatocytes lose 
      expression of hepatocyte specific genes (albumin, cytochrome P450 IIB1), acquire 
      expression of markers expressed by bile duct epithelium (cytokeratin 19), produce 
      TGFalpha and acidic FGF and assume a very simplified morphologic phenotype by 
      electron microscopy. A major change associated with this transition is the 
      decrease in ratio between transcription factors C/EBPalpha and C/EBPbeta, as well 
      as the emergence in the proliferating hepatocytes of transcription factors AP1, 
      NFkappaB. The liver associated transcription factors HNFI, HNF3, and HNF4 are 
      preserved throughout this process. After population expansion and clonal growth, 
      the proliferating hepatocytes can return to mature hepatocyte phenotype in the 
      presence of EHS gel (Matrigel). This includes complete restoration of electron 
      microscopic structure and albumin expression. The hepatocyte cultures however can 
      instead be induced to form acinar/ductular structures akin to bile ductules (in 
      the presence of HGF/SF and type I collagen). These transformations affect the 
      entire population of the hepatocytes and occur even when DNA synthesis is 
      inhibited. Similar acinar/ductular structures are seen in embryonic liver when 
      HGF/SF and its receptor are expressed at high levels. These findings strongly 
      support the hypothesis that mature hepatocytes can function as or be a source of 
      bipotential facultative hepatic stem cells (hepatoblasts). These studies also 
      provide evidence for the growth factor and matrix signals that govern these 
      complex phenotypic transitions of facultative stem cells which are crucial for 
      recovery from acute and chronic liver injury.
FAU - Block, G D
AU  - Block GD
AD  - Department of Pathology, University of Pittsburgh Medical School, Pennsylvania 
      15261, USA.
FAU - Locker, J
AU  - Locker J
FAU - Bowen, W C
AU  - Bowen WC
FAU - Petersen, B E
AU  - Petersen BE
FAU - Katyal, S
AU  - Katyal S
FAU - Strom, S C
AU  - Strom SC
FAU - Riley, T
AU  - Riley T
FAU - Howard, T A
AU  - Howard TA
FAU - Michalopoulos, G K
AU  - Michalopoulos GK
LA  - eng
GR  - AA10010/AA/NIAAA NIH HHS/United States
GR  - CA43909/CA/NCI NIH HHS/United States
GR  - HL48651/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Biomarkers)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (Drug Combinations)
RN  - 0 (Laminin)
RN  - 0 (Proteoglycans)
RN  - 0 (Transcription Factors)
RN  - 0 (Transferrin)
RN  - 0 (Transforming Growth Factor alpha)
RN  - 119978-18-6 (matrigel)
RN  - 25X51I8RD4 (Niacinamide)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 68238-35-7 (Keratins)
RN  - 9007-34-5 (Collagen)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Adult
MH  - Base Sequence
MH  - Biomarkers
MH  - Cell Differentiation/drug effects
MH  - Cell Division/drug effects
MH  - Cell Lineage
MH  - Cells, Cultured
MH  - Collagen
MH  - *Culture Media, Serum-Free
MH  - Drug Combinations
MH  - Epidermal Growth Factor/*pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Hepatocyte Growth Factor/*pharmacology
MH  - Humans
MH  - Keratins/biosynthesis/genetics
MH  - Laminin
MH  - Liver/cytology/*drug effects
MH  - Molecular Sequence Data
MH  - Morphogenesis/drug effects
MH  - Niacinamide/physiology
MH  - Phenotype
MH  - Proteoglycans
MH  - Proto-Oncogene Proteins c-met
MH  - Receptor Protein-Tyrosine Kinases/biosynthesis/genetics
MH  - Transcription Factors/biosynthesis/genetics
MH  - Transferrin/physiology
MH  - Transforming Growth Factor alpha/*pharmacology
PMC - PMC2120765
EDAT- 1996/03/01 00:00
MHDA- 1996/03/01 00:01
PMCR- 1996/09/02
CRDT- 1996/03/01 00:00
PHST- 1996/03/01 00:00 [pubmed]
PHST- 1996/03/01 00:01 [medline]
PHST- 1996/03/01 00:00 [entrez]
PHST- 1996/09/02 00:00 [pmc-release]
AID - 96176307 [pii]
AID - 10.1083/jcb.132.6.1133 [doi]
PST - ppublish
SO  - J Cell Biol. 1996 Mar;132(6):1133-49. doi: 10.1083/jcb.132.6.1133.