Increased expression of H19 non-coding mRNA follows hepatocyte proliferation in the rat and mouse

J Hepatol. 2004 May;40(5):808-14. doi: 10.1016/j.jhep.2004.01.022.

Abstract

Background/aims: H19 is a paternally imprinted gene that is believed to function as non-coding mRNA. While H19 is only faintly expressed in the normal adult liver, it is abundantly expressed during the fetal period. We explored the possibility that H19 might participate in the regulation of hepatocyte proliferation.

Methods: Adult male rats and mice were subjected to a two-thirds partial hepatectomy, and after various time periods, hepatocytes were isolated and analyzed for H19 gene expression. The expression was also examined in cultured rat hepatocytes.

Results: The expression of H19 was dramatically increased after 2 days (rat) and 4 days (mouse), peaked at 3 days (rat) and 6 days (mouse), and then gradually declined. In both species, the increase in H19 gene expression was preceded by the induction of proliferating cell nuclear antigen and DNA synthesis. An allele-specific RT-PCR analysis in the mouse showed that the paternally imprinted status of the gene was maintained after a partial hepatectomy. H19 was strongly induced in spheroid cultures after transient hepatocyte proliferation, but not in conventional monolayer cultures, in which persistent proliferation occurred.

Conclusions: Our results demonstrated that H19 gene expression was dynamically regulated in adult hepatocytes in close association with their proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Differentiation
  • Cells, Cultured
  • DNA / genetics
  • Gene Expression
  • Genomic Imprinting
  • Hepatectomy
  • Hepatocytes / cytology*
  • Hepatocytes / metabolism*
  • In Situ Hybridization
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred CBA
  • RNA, Long Noncoding
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism*
  • RNA, Untranslated / genetics*
  • Rats
  • Rats, Inbred F344

Substances

  • H19 long non-coding RNA
  • RNA, Long Noncoding
  • RNA, Messenger
  • RNA, Untranslated
  • DNA