PMID- 29366780
OWN - NLM
STAT- MEDLINE
DCOM- 20180222
LR  - 20180222
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 496
IP  - 3
DP  - 2018 Feb 12
TI  - MicroRNA-29a mitigation of toll-like receptor 2 and 4 signaling and alleviation 
      of obstructive jaundice-induced fibrosis in mice.
PG  - 880-886
LID - S0006-291X(18)30147-5 [pii]
LID - 10.1016/j.bbrc.2018.01.132 [doi]
AB  - Cholestasis and hepatitis can cause continuous liver damage that may ultimately 
      result in liver fibrosis. In a previous study, we demonstrated that microRNA-29a 
      (miR-29a) protects against liver fibrosis. Toll-like receptor 2 (TLR2) and TLR4 
      are pattern recognition receptors of bacterial lipoprotein and 
      lipopolysaccharide, both of which participate in activating hepatic stellate 
      cells and liver fibrosis. The purpose of this study is to characterize the 
      biological influence of miR-29a on TLR2 and TLR4 signaling in livers injured with 
      bile duct ligation (BDL). We performed BDL on both miR-29a transgenic mice 
      (miR-29aTg) and wild-type mice to induce cholestatic liver injury. Primary HSCs 
      were transfected with a miR-29a mimic and inhibitor. In the wild-type mice, the 
      BDL demonstrated significant alpha-smooth muscle actin fibrotic matrix formation and 
      hepatic high mobility group box-1 expression. However, in the miR-29aTg mice, 
      these factors were significantly reduced. Furthermore, miR-29a overexpression 
      reduced the BDL exaggeration of TLR2, TLR4, MyD88, bromodomain-containing protein 
      4 (BRD4), phospho-p65 as well as proinflammatory cytokines, IL-1beta, MCP-1, TGF-beta, 
      and TNF-alpha. In vitro, miR-29a mimic transfection reduced alpha-SMA, BRD4,TLR2, and 
      TLR4 expressions in HSCs. This study provides new molecular insight into the 
      ability of miR-29a to inhibit TLR2 and TLR4 signaling, which thus slows the 
      progression of cholestatic liver deterioration.
CI  - Copyright (c) 2018 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Lin, Yen-Cheng
AU  - Lin YC
AD  - Department of Pediatrics, Chiayi Chang Gung Memorial Hospital, Taiwan.
FAU - Wang, Feng-Sheng
AU  - Wang FS
AD  - Genomics and Proteomics Core Laboratory, Department of Medical Research, 
      Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College, Taiwan.
FAU - Yang, Ya-Ling
AU  - Yang YL
AD  - Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung 
      University College of Medicine, Kaohsiung, Taiwan.
FAU - Chuang, Yuan-Ting
AU  - Chuang YT
AD  - Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung 
      University College of Medicine, Kaohsiung, Taiwan.
FAU - Huang, Ying-Hsien
AU  - Huang YH
AD  - Department of Pediatrics, Chiayi Chang Gung Memorial Hospital, Taiwan; Department 
      of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University 
      College of Medicine, Kaohsiung, Taiwan. Electronic address: 
      yhhuang123@yahoo.com.tw.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180131
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Cytokines)
RN  - 0 (MIRN29 microRNA, mouse)
RN  - 0 (MicroRNAs)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Animals
MH  - Cytokines/metabolism
MH  - Jaundice, Obstructive/complications/*metabolism/pathology
MH  - Liver Cirrhosis, Biliary/complications/*metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - MicroRNAs/*metabolism
MH  - Signal Transduction
MH  - Toll-Like Receptor 2/*metabolism
MH  - Toll-Like Receptor 4/*metabolism
OTO - NOTNLM
OT  - Cholestasis
OT  - Liver fibrosis
OT  - Proinflammatory cytokines
OT  - TLR2
OT  - TLR4
OT  - miR-29a
EDAT- 2018/01/26 06:00
MHDA- 2018/02/23 06:00
CRDT- 2018/01/26 06:00
PHST- 2018/01/12 00:00 [received]
PHST- 2018/01/20 00:00 [accepted]
PHST- 2018/01/26 06:00 [pubmed]
PHST- 2018/02/23 06:00 [medline]
PHST- 2018/01/26 06:00 [entrez]
AID - S0006-291X(18)30147-5 [pii]
AID - 10.1016/j.bbrc.2018.01.132 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2018 Feb 12;496(3):880-886. doi: 
      10.1016/j.bbrc.2018.01.132. Epub 2018 Jan 31.