Age associated dysfunction of transcription factor in lung epithelial cells and COPD pathogenesis

• Project/Area Number: 18K08176
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Kyoto University
• Principal Investigator: SATO ATSUYASU 京都大学, 医学研究科, 助教 (30706677)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: COPD / C/EBPα / 老化 / 喫煙曝露 / 線毛上皮細胞 / 肺上皮

Outline of Final Research Achievements

C/EBPα, a transcription factor, is activated to protect the lung during lung injury. In senescence model, the dysfunction of C/EBPα might lead the loss of homeostasis in lung. COPD is a representative disease that chronic smoke exposure develops lung destruction and irreversible obstructive disorder in old, suggesting the strong association between senescence and COPD pathogenesis. We hypothesized that C/EBPα dysfunction associates to COPD. Those transcription factor analysis might contribute to explain the disease pathogenesis.

Academic Significance and Societal Importance of the Research Achievements

COPDは日本人にとって多くの人口を占める疾患であり、身体活動性の低下や寝たきりなど社会問題として重要な課題を多く含む。根治的な治療方法はなく、対症療法に限定され新規の治療方法が期待される。老化により欠落した因子の検討により新たな治療ターゲットが期待される。

Research Products

• [Int'l Joint Research] Boehringer Ingelheim GmbH(ドイツ)
• [Journal Article] Serine Protease Imbalance in the Small Airways and Development of Centrilobular Emphysema in Chronic Obstructive Pulmonary Disease. (2020)
  • Author(s): 4.Uemasu K, Tanabe N, Tanimura K, Hasegawa K, Mizutani T, Hamakawa Y, Sato S, Ogawa E, Thomas MJ, Ikegami M, Muro S, Hirai T, Sato A.
  • Journal Title: Am J Respir Cell Mol Biol. Volume: 63 Pages: 67-78
  • Peer Reviewed
• [Journal Article] Serine Protease Imbalance in the Small Airways and Development of Centrilobular Emphysema in COPD. (2020)
  • Author(s): Kiyoshi Uemasu, Naoya Tanabe, Kazuya Tanimura, Koichi Hasegawa, Tatsushi Mizutani, Yoko Hamakawa, Susumu Sato, Emiko Ogawa, Matthew J Thomas, Machiko Ikegami, Shigeo Muro, Toyohiro Hirai, Atsuyasu Sato
  • Journal Title: Am J Respir Cell Mol Biol. Volume: NA
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 慢性喫煙による末梢気道線毛上皮細胞傷害からの再生に及ぼすプロテアーゼ活性についての検討 (2019)
  • Author(s): 上桝潔, 佐藤篤靖, 田辺直也, 長谷川浩一, 谷村和哉, 濱川瑶子, 水谷達志, 佐藤晋, 平井豊博
  • Organizer: 日本呼吸器学会
• [Presentation] Regulation of Protease Activity in Distal Airway Is Critical for Ciliated Cell Regeneration during Chronic Cigarette Smoke Exposure (2019)
  • Author(s): Kiyoshi Uemasu, Naoya Tanabe, Kazuya Tanimura, Koichi Hasegawa, Tatsushi Mizutani, Yoko Hamakawa, Susumu Sato, Emiko Ogawa, Matthew J Thomas, Machiko Ikegami, Shigeo Muro, Toyohiro Hirai, Atsuyasu Sato
  • Organizer: American Thoracic Society 2019
  • Int'l Joint Research