Transcriptional profiling in human HaCaT keratinocytes in response to kaempferol and identification of potential transcription factors for regulating differential gene expression.
10.3858/emm.2008.40.2.208
- Author:
Byung Young KANG
1
;
Sujong KIM
;
Ki Hwan LEE
;
Yong Sung LEE
;
Il HONG
;
Mi Ock LEE
;
Daejin MIN
;
Ihseop CHANG
;
Jae Sung HWANG
;
Jun Seong PARK
;
Duck Hee KIM
;
Byung gee KIM
Author Information
1. School of Chemical and Biological Engineering, Seoul National University, Seoul 151-742, Korea. byungkim@snu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
keratinocytes;
kaempferol;
NF-kappaB;
oligonucleotide array sequence analysis;
peroxisome proliferator-activated receptors;
transcription factors
- MeSH:
Base Sequence;
Cell Line;
DNA Primers;
Enzyme-Linked Immunosorbent Assay;
*Gene Expression Profiling;
Gene Expression Regulation/*drug effects;
Humans;
Kaempferols/*pharmacology;
Keratinocytes/*drug effects/metabolism;
Oligonucleotide Array Sequence Analysis;
Promoter Regions, Genetic;
Reverse Transcriptase Polymerase Chain Reaction;
Transcription Factors/*physiology;
Transcription, Genetic/*drug effects
- From:Experimental & Molecular Medicine
2008;40(2):208-219
- CountryRepublic of Korea
- Language:English
-
Abstract:
Kaempferol is the major flavonol in green tea and exhibits many biomedically useful properties such as antioxidative, cytoprotective and anti-apoptotic activities. To elucidate its effects on the skin, we investigated the transcriptional profiles of kaempferol-treated HaCaT cells using cDNA microarray analysis and identified 147 transcripts that exhibited significant changes in expression. Of these, 18 were up-regulated and 129 were down-regulated. These transcripts were then classified into 12 categories according to their functional roles: cell adhesion/cytoskeleton, cell cycle, redox homeostasis, immune/defense responses, metabolism, protein biosynthesis/modification, intracellular transport, RNA processing, DNA modification/ replication, regulation of transcription, signal transduction and transport. We then analyzed the promoter sequences of differentially-regulated genes and identified over-represented regulatory sites and candidate transcription factors (TFs) for gene regulation by kaempferol. These included c-REL, SAP-1, Ahr-ARNT, Nrf-2, Elk-1, SPI-B, NF-kappaB and p65. In addition, we validated the microarray results and promoter analyses using conventional methods such as real-time PCR and ELISA-based transcription factor assay. Our microarray analysis has provided useful information for determining the genetic regulatory network affected by kaempferol, and this approach will be useful for elucidating gene-phytochemical interactions.