PMID- 12971963
OWN - NLM
STAT- MEDLINE
DCOM- 20040713
LR  - 20190817
IS  - 0168-8278 (Print)
IS  - 0168-8278 (Linking)
VI  - 39
IP  - 4
DP  - 2003 Oct
TI  - Oxidative stress, KLF6 and transforming growth factor-beta up-regulation 
      differentiate non-alcoholic steatohepatitis progressing to fibrosis from 
      uncomplicated steatosis in rats.
PG  - 538-46
AB  - BACKGROUND/AIMS: Pathogenesis of non-alcoholic steatohepatitis (NASH) remains 
      poorly understood. Cytochrome P450 2E1 (CYP 2E1), cytokines, oxidative stress and 
      activation of hepatic stellate cells seem to play a role in this process. The aim 
      was to determine the potential implication of these factors in the progression 
      from uncomplicated steatosis to steatohepatitis with progressive fibrosis. 
      METHODS: Animals were fed a standard diet, a 5% orotic acid-diet (OA) developing 
      hepatic steatosis, or the methionine-choline deficient (MCD) diet inducing 
      steatohepatitis for 2 and 6 weeks. Lipid peroxidation, CYP 2E1 expression and 
      activity, expression of UCP-2, interleukin (IL)-6, transforming growth factor 
      (TGF)beta1, KLF6 mRNAs, and activation of hepatic stellate cells were examined by 
      gas chromatography, high-performance liquid chromatography, Western blotting, 
      quantitative polymerase chain reaction and immunohistochemistry. RESULTS: Lipid 
      peroxidation increased in the MCD model whereas only minor changes occurred in 
      the OA model. KLF6 and TGFbeta1 mRNAs were selectively up-regulated in MCD 
      animals. Stellate cell activation, inflammation and collagen deposition only 
      occurred in the MCD group. CYP 2E1 expression and activity increased in the OA 
      group while both decreased in MCD animals. UCP-2 and IL-6 mRNA increased in both 
      groups. CONCLUSIONS: In the context of steatosis, lipid peroxidation is 
      associated with inflammation and stellate cell activation with concomitant 
      increase in TGFbeta1 production, possibly through up-regulation of KLF6.
FAU - Starkel, Peter
AU  - Starkel P
AD  - Laboratory of Gastroenterology, St. Luc University Hospital, Universite 
      Catholique de Louvain, Avenue Hippocrate 10, 1200 Brussels, Belgium.
FAU - Sempoux, Christine
AU  - Sempoux C
FAU - Leclercq, Isabelle
AU  - Leclercq I
FAU - Herin, Michel
AU  - Herin M
FAU - Deby, C
AU  - Deby C
FAU - Desager, Jean-Pierre
AU  - Desager JP
FAU - Horsmans, Yves
AU  - Horsmans Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Hepatol
JT  - Journal of hepatology
JID - 8503886
RN  - 0 (Actins)
RN  - 0 (Interleukin-6)
RN  - 0 (Ion Channels)
RN  - 0 (Klf6 protein, rat)
RN  - 0 (Kruppel-Like Factor 6)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tgfb1 protein, rat)
RN  - 0 (Trans-Activators)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Ucp2 protein, rat)
RN  - 0 (Uncoupling Protein 2)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
SB  - IM
MH  - Actins/metabolism
MH  - Animals
MH  - Cytochrome P-450 Enzyme System/metabolism
MH  - Diagnosis, Differential
MH  - Disease Progression
MH  - Fatty Liver/*complications/*diagnosis/pathology
MH  - Immunohistochemistry
MH  - Interleukin-6/genetics
MH  - Ion Channels
MH  - Kruppel-Like Factor 6
MH  - Kruppel-Like Transcription Factors
MH  - Lipid Metabolism
MH  - Lipid Peroxidation
MH  - Liver/metabolism
MH  - Liver Cirrhosis/*etiology
MH  - Male
MH  - Membrane Transport Proteins/genetics
MH  - Microsomes, Liver/metabolism
MH  - Mitochondrial Proteins/genetics
MH  - Muscle, Smooth/metabolism
MH  - *Oxidative Stress
MH  - *Proto-Oncogene Proteins
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Trans-Activators/genetics/*metabolism
MH  - Transforming Growth Factor beta/genetics/*metabolism
MH  - Transforming Growth Factor beta1
MH  - Uncoupling Protein 2
MH  - Up-Regulation
EDAT- 2003/09/16 05:00
MHDA- 2004/07/14 05:00
CRDT- 2003/09/16 05:00
PHST- 2003/09/16 05:00 [pubmed]
PHST- 2004/07/14 05:00 [medline]
PHST- 2003/09/16 05:00 [entrez]
AID - S016882780300360X [pii]
AID - 10.1016/s0168-8278(03)00360-x [doi]
PST - ppublish
SO  - J Hepatol. 2003 Oct;39(4):538-46. doi: 10.1016/s0168-8278(03)00360-x.