Comparison of (-)-epigallocatechin-3-gallate Elicited Liver and Small Intestine Gene Expression Profiles Between C57BL/6J Mice and C57BL/6J/Nrf2 (-/-) Mice

Pharm Res. 2005 Nov;22(11):1805-20. doi: 10.1007/s11095-005-7546-8. Epub 2005 Aug 16.

Abstract

Purpose: This study was conducted to study global gene expression profiles elicited by (-)-epigallocatechin-3-gallate (EGCG) in mouse liver and small intestine, as well as to identify EGCG-regulated Nrf2-dependent genes.

Methods: C57BL/6J and C57BL/6J/Nrf2(-/-) mice were given an oral dose of EGCG at 200 mg/kg or treated with vehicle. Both liver and small intestine were collected 3 h and 12 h after treatment. Total RNA was extracted from the tissues and gene expression profiles were analyzed using Affymetrix mouse genome 430 2.0 array and GeneSpring 6.1 software. Microarray data were validated using quantitative real-time reverse transcription-PCR chain reaction analysis.

Results: Genes that were either induced or suppressed more than two fold by EGCG treatment compared with vehicle treatment in the same genotype group were filtered using the GeneSpring software. Among these well-defined genes, 671 EGCG-regulated Nrf2-dependent genes and 256 EGCG-regulated Nrf2-independent genes were identified in liver, whereas 228 EGCG-regulated Nrf2-dependent genes and 98 EGCG-regulated Nrf2-independent genes were identified in the small intestine. Based on their biological functions, these genes mainly fall into the category of ubiquitination and proteolysis, electron transport, detoxification, transport, cell growth and apoptosis, cell adhesion, kinase and phosphatases, and transcription factors.

Conclusions: Genes expressed in mouse liver are more responsive to oral treatment of EGCG than those expressed in small intestine. EGCG could regulate many genes in both organs in an Nrf2-dependent manner. The identification of genes related to detoxification, transport, cell growth and apoptosis, cell adhesion, kinase, and transcription regulated by EGCG not only provide potential novel insight into the effect of EGCG on global gene expression and chemopreventive effects, but also point to the potential role of Nrf2 in these processes.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Gene Expression Profiling
  • Intestine, Small / drug effects*
  • Intestine, Small / metabolism
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-E2-Related Factor 2 / physiology*
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction

Substances

  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Catechin
  • epigallocatechin gallate