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An integrated biological approach to nuclear receptor signaling in physiological control and disease

Carsten Carlberg1, Thomas W Dunlop

  • 1Department of Biochemistry, University of Kuopio, FIN-70211 Kuopio, Finland. carlberg@messi.uku.fi

Critical Reviews in Eukaryotic Gene Expression
|April 6, 2006
PubMed

Insights

Nuclear receptors (NRs) like VDR, PPARs, and PXR sense daily molecules, influencing homeostasis and defense. Individual genetic variations (SNPs) in NRs affect disease susceptibility and can be identified using systems biology for early detection.

Area of Science:

  • Endocrinology
  • Genetics
  • Systems Biology

Background:

  • Nuclear receptors (NRs) including the vitamin D receptor (VDR), peroxisome proliferator-activated receptors (PPARs), and pregnane X receptor (PXR) are crucial sensors for dietary and environmental molecules.
  • These NRs regulate genes involved in fundamental cellular processes like homeostasis, growth, and immune defense.

Purpose of the Study:

  • To explore the network regulated by VDR, PPARs, and PXR.
  • To investigate the role of individual genetic variations, specifically small nucleotide polymorphisms (SNPs), in modulating the NR network's response to environmental factors.
  • To understand how NR network variations influence susceptibility to age-related diseases.

Main Methods:

  • Monitoring of target gene and protein expression patterns of VDR, PPARs, and PXR.
  • Analysis of resulting metabolite level changes and physiological consequences.
  • Application of high-throughput methods and multimodal approaches, including systems biology.

Main Results:

  • The expression patterns and physiological outcomes of VDR, PPARs, and PXR form a complex network.
  • Individual differences in NR network regulation are influenced by genetic variations (SNPs) in regulatory elements.
  • These genetic variations alter the cumulative impact of lifetime exposures on NR target gene expression.

Conclusions:

  • Individualized regulation of the NR network, influenced by genetic makeup, dictates susceptibility to aging-related diseases such as type 2 diabetes, atherosclerosis, cancer, and osteoporosis.
  • Systems biology approaches are valuable for analyzing the NR network and identifying critical biomarkers.
  • The study highlights the potential of systems biology for early disease detection through NR network analysis.

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