title: Transcriptional profiling in human HaCaT keratinocytes in response to kaempferol and identification of potential transcription factors for regulating differential gene expression.
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.
authors.affiliation: School of Chemical and Biological Engineering, Seoul National University, Seoul 151-742, Korea.
authors.forename: Byung Young
authors.initials: BY
authors.lastname: Kang
authors.forename: Sujong
authors.initials: S
authors.lastname: Kim
authors.forename: Ki-Hwan
authors.initials: KH
authors.lastname: Lee
authors.forename: Yong Sung
authors.initials: YS
authors.lastname: Lee
authors.forename: Il
authors.initials: I
authors.lastname: Hong
authors.forename: Mi-Ock
authors.initials: MO
authors.lastname: Lee
authors.forename: Daejin
authors.initials: D
authors.lastname: Min
authors.forename: Ihseop
authors.initials: I
authors.lastname: Chang
authors.forename: Jae Sung
authors.initials: JS
authors.lastname: Hwang
authors.forename: Jun Seong
authors.initials: JS
authors.lastname: Park
authors.forename: Duck Hee
authors.initials: DH
authors.lastname: Kim
authors.forename: Byung-gee
authors.initials: BG
authors.lastname: Kim
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D044949:Kaempferols / Q000494:pharmacology*; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D017931:DNA Primers; D044949:Kaempferols; D014157:Transcription Factors; C006552:kaempferol