Modulation of KGF-1 gene expression in oral fibroblasts by ripe areca nut extract.
BACKGROUND
Areca chewing is a common habit of Asians, leading to a high propensity for a variety of oral diseases in this population. This research aimed to study the expression level of genes in oral fibroblast cell lines in response to exposure to ripe areca nut extract (rANE).


METHODS
Fifteen oral fibroblast cell lines obtained from individuals aged 20-77 years were established. Treatment of a cell line with 40 micro g/ml rANE for 24 h was performed to achieve RNA for cDNA microarray analysis.


RESULTS
Among some 320 genes exhibiting detectable expression levels, 14 were up-regulated and 26 were down-regulated more than 2.5-fold. Semi-quantitative RT-PCR analysis suggested that up-regulation of IL-6 expression and down-regulation of PDGFR, APP-1 and KGF-1 expressions in multiple cell lines assayed, were compatible with the results of the microarray analysis. Using quantitative real-time RT-PCR analysis, a remarkable down-regulation of KGF-1 expression in response to 40 microg/ml rANE, ranging 1.5-ninefold as compared to controls, was found in 60% (9/15) of the cell lines.


CONCLUSIONS
This study established a novel toxicogenomic database for rANE. The down-regulation of KGF-1 expression in oral fibroblast cell lines potentially impairs the proliferation of overlying keratinocytes, which could partially explain the frequent epithelial atrophy observed in chronic areca chewers in vivo.
Ko
Shun-Yao
SY
Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
Lin
Shu-Chun
SC
Chang
Kuo-Wei
KW
Liu
Chung-Ji
CJ
Chang
Shu-Shin
SS
Lu
Suu-Yi
SY
Liu
Tsung-Yun
TY
D000328:Adult; D000368:Aged; D001114:Areca; D001798:Blood Proteins / Q000187:drug effects / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D005260:Female; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000187:drug effects* / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis / Q000235:genetics; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000166:cytology / Q000187:drug effects*; D020411:Oligonucleotide Array Sequence Analysis; D010936:Plant Extracts / Q000494:pharmacology*; D039102:Poly(A)-Binding Proteins / Q000187:drug effects / Q000235:genetics; D017479:Receptors, Platelet-Derived Growth Factor / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation
D001798:Blood Proteins; C496453:FGF7 protein, human; D015850:Interleukin-6; C104581:PABPC4 protein, human; D010936:Plant Extracts; D039102:Poly(A)-Binding Proteins; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D017479:Receptors, Platelet-Derived Growth Factor