Increased expression of H19 non-coding mRNA follows hepatocyte proliferation in the rat and mouse.
OBJECTIVE
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.
Yamamoto
Youhei
Y
Department of Pathology, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
Nishikawa
Yuji
Y
Tokairin
Takuo
T
Omori
Yasufumi
Y
Enomoto
Katsuhiko
K
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D015870:Gene Expression; D018392:Genomic Imprinting; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D022661:RNA, Untranslated / Q000235:genetics*; D051381:Rats; D011916:Rats, Inbred F344
C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D022661:RNA, Untranslated; D004247:DNA