A role of TDP-43, a candidate of novel transcription factor for TNF-alpha gene regulation, in the pathogenesis of periodontitis.

2013 Fiscal Year Final Research Report

• Project/Area Number: 24792332
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Periodontal dentistry
• Research Institution: The University of Tokushima
• Principal Investigator: MURATA Hiromi 徳島大学, 大学病院, 医員 (00583874)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 歯周病 / 単球 / LPS / TNF-α / TDP-43

Research Abstract

In previous study, TDP-43 was identified as a candidate of novel transcription factor for TNF-alpha gene regulation in periodontitis. The aim of this study was to investigated a role of TDP-43 in human monocytes/macrophages. TDP-43 localized constitutively in nuclei of differentiated THP-1 cells. LPS increased TDP-43 expression in nuclei of differentiated-THP-1 cells immediately. Overexpression of TDP-43 in THP-1 cells resulted in an increase of TNF-alpha gene expression. Inversely, knockdown of TDP-43 in THP-1 cells downregulated LPS-induced TNF-alpha gene expression. Moreover, it was suggested that the target region located -550 to -487 in TNF-alpha promoter bound several nuclear proteins such as TDP-43 and p65. These results have shown that TDP-43 may play a role as an up-regulator of LPS-induced TNF-alpha gene expression by acting in combination with other factors such as NF-kappaB in nuclei of monocytes and macrophages.

Research Products

• [Presentation] 低酸素環境がヒト口腔上皮細胞の各種遺伝子発現に及ぼす影響 (2013)
  • Author(s): 中島由紀子, 木戸淳一, 稲垣裕司, 板東美香, 廣島佑香, 村田裕美, 永田俊彦
  • Organizer: 第56回秋季日本歯周病学会
  • Place of Presentation: 前橋市民文化会館(群馬)
  • Year and Date: 2013-09-22
• [Presentation] 神経変性疾患関連因子 TDP-43 は単球における LPS 誘導性 TNF-α転写制御に関与する (2013)
  • Author(s): 村田裕美, 前田博史, 高柴正悟, 木戸淳一, 永田俊彦
  • Organizer: 第56回秋季日本歯周病学会
  • Place of Presentation: 前橋市民文化会館(群馬)
  • Year and Date: 2013-09-22
• [Presentation] A major neurodegenerative disease protein TDP-43 enhances TNF-α transcriptional regulation in human monocyte-derived macrophage-like cells (2013)
  • Author(s): 村田裕美, 二宮雅美, 高柴正悟, 前田博史, 木戸淳一, 永田俊彦
  • Organizer: 10th Asian Pacific Society of Periodontology Meeting
  • Place of Presentation: 奈良県新公会堂(奈良県)
  • Year and Date: 2013-09-04
• [Presentation] 神経変性疾患関連因子 TDP-43 はマクロファージ様細胞の TNF-α転写調節に関与する (2013)
  • Author(s): 村田裕美, 生田貴久, 前田博史, 高柴正悟, 木戸淳一, 永田俊彦
  • Organizer: 第138回春季日本歯科保存学会
  • Place of Presentation: 福岡国際会議場(福岡県)
  • Year and Date: 2013-06-28
• [Presentation] 姉妹に認められた広汎型侵襲性歯周炎に対して包括的歯周治療を行った症例 (2013)
  • Author(s): 二宮雅美, 板東美香, 村田裕美, 生田貴久, 木戸淳一, 永田俊彦
  • Organizer: 第56回春季日本歯周病学会
  • Place of Presentation: タワーホール船堀(東京)
  • Year and Date: 2013-05-31
• [Presentation] 糖尿病関連歯周炎の診断マーカーとしての歯肉溝滲出液中グリコアルブミンとカルプロテクチンの有用性 (2013)
  • Author(s): 木戸淳一, 板東美香, 坂東由紀子, 稲垣 裕司, 廣島佑香, 梶浦由加里, 美原智恵, 村田裕美, 生田貴久, 篠原宏貴, 橋本万里, 舟木真理, 斉藤晴比呂, 永田俊彦
  • Organizer: 第56回日本糖尿病学会
  • Place of Presentation: ホテル日航熊本(熊本県)
  • Year and Date: 2013-05-17