PMID- 30826054
OWN - NLM
STAT- MEDLINE
DCOM- 20200121
LR  - 20200121
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 511
IP  - 3
DP  - 2019 Apr 9
TI  - miR-222 regulates proliferation of primary mouse hepatocytes in vitro.
PG  - 644-649
LID - S0006-291X(19)30289-X [pii]
LID - 10.1016/j.bbrc.2019.02.093 [doi]
AB  - It is well known that hepatocytes regenerate after liver injury, although it is 
      difficult to reproduce this phenomenon in vitro. The goal of this research was to 
      determine the factors that stimulate proliferation of primary mouse hepatocytes 
      (PMHs) in vitro. We first tested knockdown (KD) of tumor protein 53 (p53) alone 
      as well as partial hepatectomy (PH, performed 72 h prior to PMHs preparation) 
      alone. However, neither intervention stimulated hepatocyte proliferation during 
      the 72-h observation period in vitro. We then tested the combination of p53 KD 
      with PH and found that these interventions together stimulated cell proliferation 
      in vitro. Under these latter conditions we analyzed gene expression of these 
      cells by mRNA sequencing (RNA-seq) and microRNA sequencing (miRNA-seq). 
      TargetScan analysis, which determines the relationship between microRNAs and gene 
      expression, found a relationship between downregulated mmu-mir-222 (miR-222) and 
      upregulated genes such as mitogen-activated protein kinase kinase kinase 2 
      (Map3k2). To confirm this relationship, we performed miR-222 KD and 
      overexpression (OE) and observed the expected changes in target gene expression. 
      Furthermore, the finding that miR-222 KD or OE stimulates or suppresses, 
      respectively, hepatocyte proliferation is well explained by the association 
      between miR-222 and its target genes, which stimulate growth. Our results suggest 
      that miR-222 is one of the key factors regulating PMH proliferation in vitro.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Higashi, Miki
AU  - Higashi M
AD  - Department of Biochemistry, Nagasaki University School of Medicine, Nagasaki, 
      Japan; Department of Physiology, Saitama Medical University, Saitama, Japan.
FAU - Yoneda, Mitsuhiro
AU  - Yoneda M
AD  - Department of Biochemistry, Nagasaki University School of Medicine, Nagasaki, 
      Japan.
FAU - Nakagawa, Takeya
AU  - Nakagawa T
AD  - Department of Biochemistry, Nagasaki University School of Medicine, Nagasaki, 
      Japan.
FAU - Ikeda, Masaaki
AU  - Ikeda M
AD  - Department of Physiology, Saitama Medical University, Saitama, Japan.
FAU - Ito, Takashi
AU  - Ito T
AD  - Department of Biochemistry, Nagasaki University School of Medicine, Nagasaki, 
      Japan. Electronic address: tito@nagasaki-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190227
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (MIRN222 microRNA, mouse)
RN  - 0 (MicroRNAs)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinase 2)
RN  - EC 2.7.11.25 (Map3k2 protein, mouse)
SB  - IM
MH  - Animals
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Down-Regulation
MH  - Hepatocytes/*cytology/metabolism
MH  - MAP Kinase Kinase Kinase 2/genetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/*genetics
MH  - Up-Regulation
OTO - NOTNLM
OT  - Hepatocyte
OT  - Map3k2
OT  - miR-222
EDAT- 2019/03/04 06:00
MHDA- 2020/01/22 06:00
CRDT- 2019/03/04 06:00
PHST- 2019/02/13 00:00 [received]
PHST- 2019/02/17 00:00 [accepted]
PHST- 2019/03/04 06:00 [pubmed]
PHST- 2020/01/22 06:00 [medline]
PHST- 2019/03/04 06:00 [entrez]
AID - S0006-291X(19)30289-X [pii]
AID - 10.1016/j.bbrc.2019.02.093 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2019 Apr 9;511(3):644-649. doi: 
      10.1016/j.bbrc.2019.02.093. Epub 2019 Feb 27.