PMID- 26042593
OWN - NLM
STAT- MEDLINE
DCOM- 20160510
LR  - 20231104
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 6
DP  - 2015
TI  - MicroRNA-155 Deficiency Attenuates Liver Steatosis and Fibrosis without Reducing 
      Inflammation in a Mouse Model of Steatohepatitis.
PG  - e0129251
LID - 10.1371/journal.pone.0129251 [doi]
LID - e0129251
AB  - BACKGROUND & AIM: MicroRNAs (miRs) regulate hepatic steatosis, inflammation and 
      fibrosis. Fibrosis is the consequence of chronic tissue damage and inflammation. 
      We hypothesized that deficiency of miR-155, a master regulator of inflammation, 
      attenuates steatohepatitis and fibrosis. METHODS: Wild type (WT) and 
      miR-155-deficient (KO) mice were fed methionine-choline-deficient (MCD) or 
      -supplemented (MCS) control diet for 5 weeks. Liver injury, inflammation, 
      steatosis and fibrosis were assessed. RESULTS: MCD diet resulted in 
      steatohepatitis and increased miR-155 expression in total liver, hepatocytes and 
      Kupffer cells. Steatosis and expression of genes involved in fatty acid 
      metabolism were attenuated in miR-155 KO mice after MCD feeding. In contrast, 
      miR-155 deficiency failed to attenuate inflammatory cell infiltration, nuclear 
      factor kappa beta (NF-kappaB) activation and enhanced the expression of the 
      pro-inflammatory cytokines tumor necrosis factor alpha (TNFalpha) and monocyte 
      chemoattractant protein-1 (MCP1) in MCD diet-fed mice. We found a significant 
      attenuation of apoptosis (cleaved caspase-3) and reduction in collagen and alpha 
      smooth muscle actin (alphaSMA) levels in miR-155 KO mice compared to WTs on MCD diet. 
      In addition, we found attenuation of platelet derived growth factor (PDGF), a 
      pro-fibrotic cytokine; SMAD family member 3 (Smad3), a protein involved in 
      transforming growth factor-beta (TGFbeta) signal transduction and vimentin, a 
      mesenchymal marker and indirect indicator of epithelial-to-mesenchymal transition 
      (EMT) in miR-155 KO mice. Nuclear binding of CCAAT enhancer binding protein beta 
      (C/EBPbeta) a miR-155 target involved in EMT was significantly increased in miR-155 
      KO compared to WT mice. CONCLUSIONS: Our novel data demonstrate that miR-155 
      deficiency can reduce steatosis and fibrosis without decreasing inflammation in 
      steatohepatitis.
FAU - Csak, Timea
AU  - Csak T
AD  - Department of Medicine, University of Massachusetts Medical School, Worcester, 
      Massachusetts, United States of America.
FAU - Bala, Shashi
AU  - Bala S
AD  - Department of Medicine, University of Massachusetts Medical School, Worcester, 
      Massachusetts, United States of America.
FAU - Lippai, Dora
AU  - Lippai D
AD  - 2nd Department of Medicine, Semmelweis University, Budapest, Hungary.
FAU - Kodys, Karen
AU  - Kodys K
AD  - Department of Medicine, University of Massachusetts Medical School, Worcester, 
      Massachusetts, United States of America.
FAU - Catalano, Donna
AU  - Catalano D
AD  - Department of Medicine, University of Massachusetts Medical School, Worcester, 
      Massachusetts, United States of America.
FAU - Iracheta-Vellve, Arvin
AU  - Iracheta-Vellve A
AD  - Department of Medicine, University of Massachusetts Medical School, Worcester, 
      Massachusetts, United States of America.
FAU - Szabo, Gyongyi
AU  - Szabo G
AD  - Department of Medicine, University of Massachusetts Medical School, Worcester, 
      Massachusetts, United States of America.
LA  - eng
GR  - R01 AA020744/AA/NIAAA NIH HHS/United States
GR  - AA020744/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20150604
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (CCAAT-Enhancer-Binding Protein-beta)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn155 microRNA, mouse)
RN  - 0 (Smad3 Protein)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vimentin)
RN  - AE28F7PNPL (Methionine)
RN  - N91BDP6H0X (Choline)
SB  - IM
MH  - Animals
MH  - CCAAT-Enhancer-Binding Protein-beta/metabolism
MH  - Cell Nucleus/metabolism
MH  - Choline
MH  - Diet
MH  - Disease Models, Animal
MH  - Fatty Liver/*complications/*genetics
MH  - Female
MH  - Gene Expression Regulation
MH  - Inflammation/*complications
MH  - Lipid Metabolism/genetics
MH  - Lipopolysaccharides/pharmacology
MH  - Liver/pathology
MH  - Liver Cirrhosis/*complications/*genetics
MH  - Methionine
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/genetics/*metabolism
MH  - Protein Binding
MH  - Smad3 Protein/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Vimentin/metabolism
PMC - PMC4456142
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/06/05 06:00
MHDA- 2016/05/11 06:00
PMCR- 2015/06/04
CRDT- 2015/06/05 06:00
PHST- 2014/11/12 00:00 [received]
PHST- 2015/05/06 00:00 [accepted]
PHST- 2015/06/05 06:00 [entrez]
PHST- 2015/06/05 06:00 [pubmed]
PHST- 2016/05/11 06:00 [medline]
PHST- 2015/06/04 00:00 [pmc-release]
AID - PONE-D-14-50956 [pii]
AID - 10.1371/journal.pone.0129251 [doi]
PST - epublish
SO  - PLoS One. 2015 Jun 4;10(6):e0129251. doi: 10.1371/journal.pone.0129251. 
      eCollection 2015.