PMID- 12815367
OWN - NLM
STAT- MEDLINE
DCOM- 20040407
LR  - 20191210
IS  - 1470-269X (Print)
IS  - 1470-269X (Linking)
VI  - 3
IP  - 3
DP  - 2003
TI  - Target validation in hypoxia-induced vascular remodeling using 
      transcriptome/metabolome analysis.
PG  - 183-8
AB  - The present study describes combined transcriptome and metabolome analysis for 
      therapeutic target validation in hypoxia-induced vascular remodeling. Exposure to 
      hypoxic conditions resulted in the upregulation of S100C mRNA and increased 
      taurine (2-aminoethanesulfonic acid) content in the rat lung, as demonstrated by 
      differential display and amino-acid content analysis. Hypoxia resulted in 
      transcriptional activation of the S100C promoter through hypoxia-inducible 
      factor-1 (HIF-1). Taurine suppressed HIF-1-mediated increases in S100C 
      transcription. Moreover, oral taurine administration attenuated vascular 
      remodeling in hypoxic rat lung, whereas depletion of endogenous taurine by 
      administration of beta-alanine resulted in increased vascular remodeling. 
      Inhibition of HIF transcription by taurine may be of therapeutic benefit in 
      preventing hypoxia-induced vascular remodeling. In conclusion, we used 
      transcriptome and metabolome analysis to identify a therapeutic 
      low-molecular-weight ligand that plays a critical role in hypoxia-induced 
      vascular remodeling. These techniques provided an excellent strategy for 
      screening and validation of targets.
FAU - Amano, H
AU  - Amano H
AD  - Department of Molecular and Cellular Pharmacology, Mie University School of 
      Medicine, Tsu, Mie, Japan.
FAU - Maruyama, K
AU  - Maruyama K
FAU - Naka, M
AU  - Naka M
FAU - Tanaka, T
AU  - Tanaka T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Validation Study
PL  - United States
TA  - Pharmacogenomics J
JT  - The pharmacogenomics journal
JID - 101083949
RN  - 0 (S100 Proteins)
RN  - 146909-89-9 (S100A11 protein, human)
RN  - 1EQV5MLY3D (Taurine)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cells, Cultured
MH  - Gene Expression Profiling/*methods
MH  - Gene Targeting/methods
MH  - Hypoxia/*genetics/metabolism
MH  - Lung/drug effects/metabolism
MH  - Male
MH  - Molecular Sequence Data
MH  - Muscle, Smooth, Vascular/drug effects/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - S100 Proteins/biosynthesis/*genetics
MH  - Taurine/biosynthesis/genetics/pharmacology
MH  - *Transcription, Genetic
EDAT- 2003/06/20 05:00
MHDA- 2004/04/08 05:00
CRDT- 2003/06/20 05:00
PHST- 2003/06/20 05:00 [pubmed]
PHST- 2004/04/08 05:00 [medline]
PHST- 2003/06/20 05:00 [entrez]
AID - 6500177 [pii]
AID - 10.1038/sj.tpj.6500177 [doi]
PST - ppublish
SO  - Pharmacogenomics J. 2003;3(3):183-8. doi: 10.1038/sj.tpj.6500177.