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論文情報
タイトル
Suppression of Transcription Factor PDX-1/IPF1/STF-1/IDX-1 Causes No Decrease in Insulin mRNA in MIN6 Cells
別タイトル
nichi , Yamasaki, Yoshimitsu
著者
Kajimoto, Yoshitaka
Kajimoto, Yoshitaka
Watada, Hirotaka
Watada, Hirotaka
Matsuoka, Taka-aki
Matsuoka, Taka-aki
Kaneto, Hideaki
Kaneto, Hideaki
Fujitani, Yoshio
Fujitani, Yoshio
Miyazaki, Jun-ichi
Miyazaki, Jun-ichi
Yamasaki, Yoshimitsu
Yamasaki, Yoshimitsu
キーワード等
gene expression regulation
transcription factors
homeodomain protein
antisense oligodeoxynucleotide
抄録
The insulin gene transcription factor PDX-1/IPF1/STF-1/ IDX-1 plays a key role in directing beta cell-specific gene expressions. Recently, impairment of PDX-1 expression or activity has been observed in beta cell-derived HIT cells cultured under high glucose concentrations, and this has been suggested as a possible cause of the decrease in insulin gene transcription. To investigate the pathophysiological significance of PDX-1 as a determinant of the rate of insulin gene transcription, we suppressed its expression in beta cell-derived MIN6 cells using an antisense oligodeoxynucleotide (ODN) and searched for possible changes in the beta cell-specific gene expression. Treatment of MIN6 cells with an 18-mer phosphorothioate ODN complementary to a sequence starting at the translation initiation codon of PDX-1 caused a potent, concentration-dependent reduction in PDX-1 expression; addition of 2 microM antisense ODN could reduce PDX-1 expression to 14+/-4% of the control. There was also a decrease in its DNA binding to the insulin gene A element. Despite such suppression of PDX-1, Northern blot analysis revealed no decrease in the amount of insulin mRNA in the MIN6 cells. Similarly, no changes were detected in the transcription of the glucokinase or islet amyloid polypeptide gene, for which PDX-1 was shown to function as a transcription factor. Thus, our findings dispute the physiological significance of PDX-1 in determining the rate of insulin gene transcription. This means that other components constituting the transcription-controlling machinery need to be evaluated in order to understand the molecular basis of impaired insulin biosynthesis such as that observed due to glucose toxicity.
公開者
American Society for Clinical Investigation
掲載誌名
Journal of Clinical Investigation
巻
100
号
7
開始ページ
1840
終了ページ
1846
刊行年月
1997-10
ISSN
00219738
NCID
AA00695520
DOI (出版社版)
info:doi/10.1172/JCI119712
URL
http://hdl.handle.net/11094/23107
権利情報
Copyright © 1997 The American Society for Clinical Investigation
言語
英語
カテゴリ
学術雑誌論文 Journal Article
論文詳細を表示
著者版フラグ
publisher
NII資源タイプ
学術雑誌論文
ローカル資源タイプ
学術雑誌論文
dcmi資源タイプ
text
DCTERMS.bibliographicCitation
Journal of Clinical Investigation.100(7) P.1840-P.1846
DC.title
Suppression of Transcription Factor PDX-1/IPF1/STF-1/IDX-1 Causes No Decrease in Insulin mRNA in MIN6 Cells
DCTERMS.alternative
nichi , Yamasaki, Yoshimitsu
DC.creator
Kajimoto, Yoshitaka
Watada, Hirotaka
Matsuoka, Taka-aki
Kaneto, Hideaki
Fujitani, Yoshio
Miyazaki, Jun-ichi
Yamasaki, Yoshimitsu
DC.publisher
American Society for Clinical Investigation
DC.language" scheme="DCTERMS.RFC1766
英語
DCTERMS.issued" scheme="DCTERMS.W3CDTF
1997-10
DC.identifier
info:doi/10.1172/JCI119712
DC.identifier" scheme="DCTERMS.URI
http://hdl.handle.net/11094/23107
DC.subject
gene expression regulation
transcription factors
homeodomain protein
antisense oligodeoxynucleotide
DCTERMS.abstract
The insulin gene transcription factor PDX-1/IPF1/STF-1/ IDX-1 plays a key role in directing beta cell-specific gene expressions. Recently, impairment of PDX-1 expression or activity has been observed in beta cell-derived HIT cells cultured under high glucose concentrations, and this has been suggested as a possible cause of the decrease in insulin gene transcription. To investigate the pathophysiological significance of PDX-1 as a determinant of the rate of insulin gene transcription, we suppressed its expression in beta cell-derived MIN6 cells using an antisense oligodeoxynucleotide (ODN) and searched for possible changes in the beta cell-specific gene expression. Treatment of MIN6 cells with an 18-mer phosphorothioate ODN complementary to a sequence starting at the translation initiation codon of PDX-1 caused a potent, concentration-dependent reduction in PDX-1 expression; addition of 2 microM antisense ODN could reduce PDX-1 expression to 14+/-4% of the control. There was also a decrease in its DNA binding to the insulin gene A element. Despite such suppression of PDX-1, Northern blot analysis revealed no decrease in the amount of insulin mRNA in the MIN6 cells. Similarly, no changes were detected in the transcription of the glucokinase or islet amyloid polypeptide gene, for which PDX-1 was shown to function as a transcription factor. Thus, our findings dispute the physiological significance of PDX-1 in determining the rate of insulin gene transcription. This means that other components constituting the transcription-controlling machinery need to be evaluated in order to understand the molecular basis of impaired insulin biosynthesis such as that observed due to glucose toxicity.
DC.rights
Copyright © 1997 The American Society for Clinical Investigation
citation_title
Suppression of Transcription Factor PDX-1/IPF1/STF-1/IDX-1 Causes No Decrease in Insulin mRNA in MIN6 Cells
citation_author
Kajimoto, Yoshitaka
Watada, Hirotaka
Matsuoka, Taka-aki
Kaneto, Hideaki
Fujitani, Yoshio
Miyazaki, Jun-ichi
Yamasaki, Yoshimitsu
citation_publisher
American Society for Clinical Investigation
citation_language
英語
citation_date
1997-10
citation_journal_title
Journal of Clinical Investigation
citation_volume
100
citation_issue
7
citation_firstpage
1840
citation_lastpage
1846
citation_issn
00219738
citation_doi
info:doi/10.1172/JCI119712
citation_public_url
http://hdl.handle.net/11094/23107
citation_keywords
gene expression regulation
transcription factors
homeodomain protein
antisense oligodeoxynucleotide