PMID- 26636761
OWN - NLM
STAT- MEDLINE
DCOM- 20160617
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 12
DP  - 2015
TI  - MicroRNA-122 Inhibits the Production of Inflammatory Cytokines by Targeting the 
      PKR Activator PACT in Human Hepatic Stellate Cells.
PG  - e0144295
LID - 10.1371/journal.pone.0144295 [doi]
LID - e0144295
AB  - MicroRNA-122 (miR-122) is one of the most abundant miRs in the liver. Previous 
      studies have demonstrated that miR-122 plays a role in inflammation in the liver 
      and functions in hepatic stellate cells (HSCs), which reside in the space of 
      Disse. Here, we showed that the transient inhibition of PKR-activating protein 
      (PACT) expression, by miR-122 or siRNA targeting of PACT, suppressed the 
      production of proinflammatory cytokines, such as interleukin (IL)-6, monocyte 
      chemoattractant protein-1 (MCP-1) and IL-1beta, in human HSC LX-2. Sequence and 
      functional analyses confirmed that miR-122 directly targeted the 3'-untranslated 
      region of PACT. Immunofluorescence analysis revealed that miR-122 blocked 
      NF-kappaB-nuclear translocation in LX-2 cells. We also showed that conditioned medium 
      from miR-122-transfected LX-2 cells suppressed human monocyte-derived THP-1 cell 
      migration. Taken together, our study indicates that miR-122 may downregulate 
      cytokine production in HSCs and macrophage chemotaxis and that the targeting of 
      miR-122 may have therapeutic potential for preventing the progression of liver 
      diseases.
FAU - Nakamura, Masato
AU  - Nakamura M
AD  - Department of Gastroenterology and Nephrology, Chiba University, Graduate School 
      of Medicine, Chiba, 260-8677, Japan.
FAU - Kanda, Tatsuo
AU  - Kanda T
AD  - Department of Gastroenterology and Nephrology, Chiba University, Graduate School 
      of Medicine, Chiba, 260-8677, Japan.
FAU - Sasaki, Reina
AU  - Sasaki R
AD  - Department of Gastroenterology and Nephrology, Chiba University, Graduate School 
      of Medicine, Chiba, 260-8677, Japan.
FAU - Haga, Yuki
AU  - Haga Y
AD  - Department of Gastroenterology and Nephrology, Chiba University, Graduate School 
      of Medicine, Chiba, 260-8677, Japan.
FAU - Jiang, Xia
AU  - Jiang X
AD  - Department of Gastroenterology and Nephrology, Chiba University, Graduate School 
      of Medicine, Chiba, 260-8677, Japan.
FAU - Wu, Shuang
AU  - Wu S
AD  - Department of Gastroenterology and Nephrology, Chiba University, Graduate School 
      of Medicine, Chiba, 260-8677, Japan.
FAU - Nakamoto, Shingo
AU  - Nakamoto S
AD  - Department of Gastroenterology and Nephrology, Chiba University, Graduate School 
      of Medicine, Chiba, 260-8677, Japan.
AD  - Department of Molecular Virology, Chiba University, Graduate School of Medicine, 
      Chiba, 260-8677, Japan.
FAU - Yokosuka, Osamu
AU  - Yokosuka O
AD  - Department of Gastroenterology and Nephrology, Chiba University, Graduate School 
      of Medicine, Chiba, 260-8677, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151204
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cytokines)
RN  - 0 (MIRN122 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (NF-kappa B)
RN  - 0 (PRKRA protein, human)
RN  - 0 (RNA-Binding Proteins)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Cell Line, Tumor
MH  - Cell Nucleus/genetics/*metabolism
MH  - Chemotaxis/genetics
MH  - Coculture Techniques
MH  - Cytokines/genetics/*metabolism
MH  - Hepatic Stellate Cells/*metabolism
MH  - Humans
MH  - Inflammation/genetics/metabolism
MH  - Macrophages/metabolism
MH  - MicroRNAs/genetics/*metabolism
MH  - NF-kappa B/genetics/metabolism
MH  - RNA-Binding Proteins/genetics/*metabolism
PMC - PMC4670168
COIS- Competing Interests: TK received lecture fees from Chugai Pharmaceutical, MSD, 
      Tanabe-Mitsubishi, Daiichi-Sankyo, and Bristol-Myers Squibb, and a research grant 
      from Chugai. OY received grant support from Chugai Pharmaceutical, Bayer, MSD, 
      Daiichi-Sankyo, Tanabe-Mitsubishi, and Bristol-Myers Squibb. The other authors 
      have declared that no competing interests exist. These do not alter the authors' 
      adherence to PLOS ONE policies on sharing data and materials.
EDAT- 2015/12/05 06:00
MHDA- 2016/06/18 06:00
PMCR- 2015/12/04
CRDT- 2015/12/05 06:00
PHST- 2015/10/01 00:00 [received]
PHST- 2015/11/16 00:00 [accepted]
PHST- 2015/12/05 06:00 [entrez]
PHST- 2015/12/05 06:00 [pubmed]
PHST- 2016/06/18 06:00 [medline]
PHST- 2015/12/04 00:00 [pmc-release]
AID - PONE-D-15-43229 [pii]
AID - 10.1371/journal.pone.0144295 [doi]
PST - epublish
SO  - PLoS One. 2015 Dec 4;10(12):e0144295. doi: 10.1371/journal.pone.0144295. 
      eCollection 2015.