TRANSCRIPTION FACTOR AND LIVER-SPECIFIC MESSENGER-RNA EXPRESSION IN FACULTATIVE EPITHELIAL PROGENITOR CELLS OF LIVER AND PANCREAS

The pattern of mRNA expression for liver-specific proteins and liver-e nriched transcription factors was studied in two models of facultative gut epithelial progenitor cells activation: D-galactosamine (GalN)-in duced liver injury and dietary copper depletion leading to pancreatic acinar atrophy. After 5 weeks of copper deficiency (CuD), pancreatic a cini of Fischer 344 rats underwent atrophy, associated with intense pr oliferation of small ductlike cells with oval-shaped nuclei. These cel ls resemble morphologically epithelial progenitor cells of the liver t hat proliferate after GalN administration. Activated pancreatic epithe lial cells express mRNAs for liver-specific genes normally expressed i n fetal liver, including alpha-fetoprotein, albumin, alpha-1 antitryps in, glucose-6-phosphatase, and others, but not genes that are turned o n after birth such as serine dehydratase, tyrosine aminotransferase, a nd multidrug resistance gene-1b. The express mRNAs for liver-enriched transcription factors including HNF-1 alpha, HNF-3 beta and gamma, HNF -4, and members of the CCAAT-enhancer binding protein (C/EBP) family. The only mRNA for a liver-enriched transcription factor not detected i n the pancreas of CuD animals was HNF-3 alpha Expression of HNF-3 alph a, beta, and gamma, and C/EBP-beta mRNA was highly activated in prolif erating liver epithelial cells on days 2 and 3 after GalN injury. Incr eased expression of C/EBP-delta was observed first in the liver on day 1 after GalN administration and in the pancreas at 4 weeks after init iating CuD. We suggest that C/EBP-delta could be involved in the initi al activation of epithelial progenitor cells and that HNF-3 alpha, bet a, and gamma, and C/EBP-beta might participate in their maturation. We conclude further that pancreatic epithelial progenitor cells undertak e differentiation through the hepatocyte lineage but cannot complete t he differentiation program within the pancreatic milieu.