Target validation in hypoxia-induced vascular remodeling using transcriptome/metabolome analysis
Open Access
- 1 January 2003
- journal article
- research article
- Published by Springer Science and Business Media LLC in The Pharmacogenomics Journal
- Vol. 3 (3), 183-188
- https://doi.org/10.1038/sj.tpj.6500177
Abstract
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.Keywords
This publication has 20 references indexed in Scilit:
- Hypoxia reversibly inhibits epithelial sodium transport but does not inhibit lung ENaC or Na-K-ATPase expressionAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2003
- Effect of ischemia, calcium depletion and repletion, acidosis and hypoxia on cellular taurine content.Amino Acids, 2002
- Transcriptome meets metabolome: hierarchical and metabolic regulation of the glycolytic pathwayFEBS Letters, 2001
- Heme oxygenase-1 gene induction as an intrinsic regulation against delayed cerebral vasospasm in ratsJCI Insight, 1999
- Impaired physiological responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1αJCI Insight, 1999
- A Unique Exon–Intron Organization of a Porcine S100C Gene: Close Evolutionary Relationship to Calmodulin GenesBiochemical and Biophysical Research Communications, 1998
- Purification and characterization of a novel calcium-binding protein, S100C, from porcine heartBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1994
- Fluorescent differential display: Arbitrarily primed RT‐PCR fingerprinting on an automated DNA sequencerFEBS Letters, 1994
- Differential Display of Eukaryotic Messenger RNA by Means of the Polymerase Chain ReactionScience, 1992
- Molecular cloning and expression of the cDNA coding for a new member of the S100 protein family from porcine cardiac muscleFEBS Letters, 1991