PMID- 9124579
OWN - NLM
STAT- MEDLINE
DCOM- 19970424
LR  - 20171213
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 272
IP  - 3 Pt 1
DP  - 1997 Mar
TI  - Diminished retinoic acid signaling in hepatic stellate cells in cholestatic liver 
      fibrosis.
PG  - G589-96
AB  - Hepatic stellate cells (HSC) participate in liver fibrogenesis via 
      myofibroblastic activation, the extent of which appears to correlate with the 
      loss of cellular vitamin A. The present study has tested a hypothesis that HSC 
      activation is associated with diminished retinoic acid (RA) signaling. Pure HSC 
      were isolated from rats with cholestatic liver fibrosis induced by bile duct 
      ligation (BDL) and sham-operated animals (Sham). Northern blot analysis of HSC 
      RNA from BDL confirmed fibrogenic activation of the cells with enhanced mRNA 
      levels for procollagen-alpha1(I) and transforming growth factor-beta1 
      (TGF-beta1). Competitive polymerase chain reaction analysis showed selective 
      reductions in the mRNA levels of RA receptor (RAR)-beta and retinoid X receptor 
      (RXR)-alpha to 20 and 17% of the Sham HSC. The mRNA level for cellular retinol 
      binding protein I, a gene with RA responsive element (RARE), was also suppressed 
      by 78% in BDL. The concentrations of all-trans-RA and 9-cis-RA were decreased in 
      HSC from BDL. Nuclear extracts of these cells showed diminished binding activity 
      to the RARE, whereas activity of AP-1, a transcription factor known to be 
      antagonized by RAR and RXR, was enhanced. These results demonstrate diminished RA 
      signaling in HSC from cholestatic liver fibrosis, which appeared to have resulted 
      from RA deficiency and suppressed expression of RAR-beta and RXR-alpha. 
      Furthermore, the reciprocal enhancement of AP-1 activity and coordinately 
      increased expression of an AP-1 responsive gene, TGF-beta1, suggest a permissive 
      role of the diminished RA signaling in promoting AP-1 activity and TGF-beta1 
      expression.
FAU - Ohata, M
AU  - Ohata M
AD  - Division of Gastrointestinal and Liver Diseases, University of Southern 
      California School of Medicine and Veterans Affairs Outpatient Clinic, Los Angeles 
      90033-4581, USA.
FAU - Lin, M
AU  - Lin M
FAU - Satre, M
AU  - Satre M
FAU - Tsukamoto, H
AU  - Tsukamoto H
LA  - eng
GR  - AA-06603/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol
JT  - The American journal of physiology
JID - 0370511
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Procollagen)
RN  - 0 (RNA, Messenger)
RN  - 0 (Rbp1 protein, rat)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Retinol-Binding Proteins)
RN  - 0 (Retinol-Binding Proteins, Cellular)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Transcription Factors)
RN  - 0 (Transforming Growth Factor beta)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cholestasis/*physiopathology
MH  - DNA-Binding Proteins/metabolism
MH  - Liver/cytology/*physiopathology
MH  - Liver Cirrhosis, Biliary/*physiopathology
MH  - Male
MH  - Molecular Sequence Data
MH  - Procollagen/genetics
MH  - RNA, Messenger/genetics
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Retinoic Acid/genetics/*physiology
MH  - Retinoid X Receptors
MH  - Retinol-Binding Proteins/genetics
MH  - Retinol-Binding Proteins, Cellular
MH  - Signal Transduction
MH  - Transcription Factor AP-1/metabolism
MH  - Transcription Factors/genetics
MH  - Transforming Growth Factor beta/genetics
MH  - Tretinoin/*physiology
MH  - Up-Regulation
EDAT- 1997/03/01 00:00
MHDA- 1997/03/01 00:01
CRDT- 1997/03/01 00:00
PHST- 1997/03/01 00:00 [pubmed]
PHST- 1997/03/01 00:01 [medline]
PHST- 1997/03/01 00:00 [entrez]
AID - 10.1152/ajpgi.1997.272.3.G589 [doi]
PST - ppublish
SO  - Am J Physiol. 1997 Mar;272(3 Pt 1):G589-96. doi: 10.1152/ajpgi.1997.272.3.G589.