PMID- 20890893
OWN - NLM
STAT- MEDLINE
DCOM- 20110302
LR  - 20220408
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Linking)
VI  - 53
IP  - 1
DP  - 2011 Jan
TI  - Micro-RNA profiling reveals a role for miR-29 in human and murine liver fibrosis.
PG  - 209-18
LID - 10.1002/hep.23922 [doi]
AB  - Liver fibrosis is orchestrated by a complex network of signaling pathways 
      regulating the deposition of extracellular matrix proteins during fibrogenesis. 
      MicroRNAs (miRNAs) represent a family of small noncoding RNAs controlling 
      translation and transcription of many genes. Recently, miRNAs have been suggested 
      to crucially modulate cellular processes in the liver such as 
      hepatocarcinogenesis. However, their role in liver fibrosis is not well 
      understood. We systematically analyzed the regulation of miRNAs in a mouse model 
      of carbon tetrachloride-induced hepatic fibrogenesis (CCl(4) ) by gene array 
      analysis, which revealed a panel of miRNA that were specifically regulated in 
      livers of mice undergoing hepatic fibrosis. Within those, all three members of 
      the miR-29-family were significantly down-regulated in livers of CCl(4) -treated 
      mice as well as in mice that underwent bile duct ligation. Specific regulation of 
      miR-29 members in murine fibrosis models correlated with lower expression of 
      miR-29 in livers from patients with advanced liver fibrosis. Moreover, patients 
      with advanced liver cirrhosis showed significantly lower levels of miR-29a in 
      their serum when compared with healthy controls or patients with early fibrosis. 
      On a cellular level, down-regulation of miR-29 in murine hepatic stellate cells 
      (HSCs) was mediated by transforming growth factor beta (TGF-beta) as well as 
      inflammatory signals, namely, lipopolysaccharide (LPS) and nuclear factor kappa B 
      (NF-kappaB). Furthermore, overexpression of miR-29b in murine HSC resulted in 
      down-regulation of collagen expression. CONCLUSION: Our data indicate that miR-29 
      mediates the regulation of liver fibrosis and is part of a signaling nexus 
      involving TGF-beta- and NF-kappaB-dependent down-regulation of miR-29 family members in 
      HSC with subsequent up-regulation of extracellular matrix genes. Thus they may 
      represent targets for novel therapeutic strategies against hepatic fibrogenesis 
      and also might evolve as biomarkers in the diagnosis of liver fibrosis.
CI  - Copyright (c) 2010 American Association for the Study of Liver Diseases.
FAU - Roderburg, Christoph
AU  - Roderburg C
AD  - Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
FAU - Urban, Gerd-Willem
AU  - Urban GW
FAU - Bettermann, Kira
AU  - Bettermann K
FAU - Vucur, Mihael
AU  - Vucur M
FAU - Zimmermann, Henning
AU  - Zimmermann H
FAU - Schmidt, Sabine
AU  - Schmidt S
FAU - Janssen, Jorn
AU  - Janssen J
FAU - Koppe, Christiane
AU  - Koppe C
FAU - Knolle, Percy
AU  - Knolle P
FAU - Castoldi, Mirco
AU  - Castoldi M
FAU - Tacke, Frank
AU  - Tacke F
FAU - Trautwein, Christian
AU  - Trautwein C
FAU - Luedde, Tom
AU  - Luedde T
LA  - eng
GR  - 208237/ERC_/European Research Council/International
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101001
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - 0 (Lipopolysaccharides)
RN  - 0 (MIRN29 microRNA, mouse)
RN  - 0 (MIRN29a microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (NF-kappa B)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
CIN - Hepatology. 2011 Jan;53(1):4-6. PMID: 21254156
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Animals
MH  - Bile Ducts/physiology
MH  - Carbon Tetrachloride Poisoning/physiopathology
MH  - Disease Models, Animal
MH  - Down-Regulation
MH  - Extracellular Matrix/genetics
MH  - Female
MH  - Hepatic Stellate Cells/metabolism
MH  - Humans
MH  - Ligation
MH  - Lipopolysaccharides/pharmacology
MH  - Liver Cirrhosis/*genetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - MicroRNAs/*genetics
MH  - Middle Aged
MH  - NF-kappa B/physiology
MH  - Transforming Growth Factor beta/physiology
EDAT- 2010/10/05 06:00
MHDA- 2011/03/03 06:00
CRDT- 2010/10/05 06:00
PHST- 2010/03/18 00:00 [received]
PHST- 2010/08/06 00:00 [accepted]
PHST- 2010/10/05 06:00 [entrez]
PHST- 2010/10/05 06:00 [pubmed]
PHST- 2011/03/03 06:00 [medline]
AID - 10.1002/hep.23922 [doi]
PST - ppublish
SO  - Hepatology. 2011 Jan;53(1):209-18. doi: 10.1002/hep.23922. Epub 2010 Oct 1.