ALTERATION OF EXPRESSION OF LIVER-ENRICHED TRANSCRIPTION FACTORS IN THE TRANSITION BETWEEN GROWTH AND DIFFERENTIATION OF PRIMARY CULTURED RAT HEPATOCYTES

Citation
T. Mizuguchi et al., ALTERATION OF EXPRESSION OF LIVER-ENRICHED TRANSCRIPTION FACTORS IN THE TRANSITION BETWEEN GROWTH AND DIFFERENTIATION OF PRIMARY CULTURED RAT HEPATOCYTES, Journal of cellular physiology, 174(3), 1998, pp. 273-284
Citations number
65
Categorie Soggetti
Cell Biology
ISSN journal
00219541
Volume
174
Issue
3
Year of publication
1998
Pages
273 - 284
Database
ISI
SICI code
0021-9541(1998)174:3<273:AOEOLT>2.0.ZU;2-L
Abstract
In the present study, we showed the role of the liver-enriched transcr iption factors in the transition during which proliferating hepatocyte s become quiescent. We used primary rat hepatocytes cultured in modifi ed L-15 medium. The cells proliferated and, after the addition of 2% d imethyl sulfoxide (DMSO) from day 4, they stopped growing and graduall y differentiated. During hepatic proliferation, expression of hepatocy te nuclear factors (HNF)1 alpha, HNF4, C/EBP alpha, and C/EBP beta mRN As was depressed, whereas that of HNF3 alpha and HNF3 beta transcripts was enhanced. After the addition of DMSO, the expression of HNF1 alph a, HNF3 gamma, and HNF4 returned to the level in isolated cells and HN F1 beta mRNA expression gradually increased. However, expression of C/ EBP alpha and C/EBP beta mRNAs was partially recovered. The mitoinhibi tory agents, IL-1 beta, IL-6, TGF-beta, and activin A, were examined t o determine whether they could induce differentiation of proliferating hepatocytes as shown in cells treated with DMSO. Although these facto rs inhibited cell growth, the cells did not differentiate. The express ion pattern of HNF3 gamma mRNA was quite different in the cells cultur ed with DMSO and those cultured with cytokines. Therefore, hepatic dif ferentiation requires not only inhibition of DNA synthesis but also in duction of appropriate transcription factors. Thus; expression of HNF3 gamma, C/EBP alpha, and C/EBP beta may be necessary for hepatocytes t o acquire highly differentiated functions in addition to coexpression of certain amounts of transcripts of HNF1 alpha, HNF1 beta, HNF3 alpha , HNF3 beta, and HNF4 as well as suppression of C/EBP delta. (C) 1998 Wiley-Liss, Inc.