Molecular Target of Regenerative Pulmonary Medicine for Chronic Obstructive Pulmonary Disease

2012 Fiscal Year Final Research Report

• Project/Area Number: 23659431
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Nagoya University
• Principal Investigator: HASEGAWA Yoshinori 名古屋大学, 医学系研究科, 教授 (20270986)
• Co-Investigator(Kenkyū-buntansha): HASHIMOTO Naozumi 名古屋大学, 医学部附属病院, 病院講師 (30378020)
• Project Period (FY): 2011 – 2012
• Keywords: 肺の再生 / 低酸素 / PTEN / 組織微小環境 / 上皮間葉系移行

Research Abstract

To accumulate the basic research findings for pulmonary tissueregeneration, we focused on the molecular analysis of the Epithelial-mesenchymal transition (EMT) and its reverse phenomenon (MET). One is Twist, and the other is the effects of prolonged tissue hypoxia on EMT. We found that persistent hypoxia induced de novo twist expression, causing repression of SP-D and acquisition of an EMT phenotype. Third is tissue microenvironment (TM). In TM, many kinds of signaling pathway, which PTEN negatively regulates, are activated. Nevertheless, whether or not persistent hypoxia could affect the PTEN activity remains elusive. In this study, persistent hypoxia caused a decrease in PTEN expression and an increase in p-PTEN/PTEN ration in alveolar cells in vitro and in vivo. These findings suggest that regulation ofprolonged tissue hypoxia and EMT might be important for tissue regeneration of the lung.

Research Products

• [Journal Article] Involvement of the transcription factor twist in phenotype alteration through epithelial-mesenchymal transition in lung cancer cells (2012)
  • Author(s): Nakashima H, Hashimoto N, Aoyama D, Kohnoh T, Sakamoto K, Kusunose M, Imaizumi K, Takeyama Y, Sato M, Kawabe T, Hasegawa Y
  • Journal Title: Mol Carcinog Volume: 51 Pages: 400-10
  • Peer Reviewed
• [Journal Article] Differential modulation of surfactant protein D under acute and persistent hypoxia in acute lung injury (2012)
  • Author(s): Sakamoto K, Hashimoto N, Kondoh Y, Imaizumi K, Aoyama D, Kohnoh T, Kusunose M, Kimura M, Kawabe T, Taniguchi H, Hasegawa Y
  • Journal Title: Am J Physiol Lung Cell Mol Physiol. Volume: 303 Pages: L43-L53
  • Peer Reviewed
• [Journal Article] Emerging evidence of epithelial-to-mesenchymal transition in lung carcinogenesis (2012)
  • Author(s): Sato M, Shames DS, Hasegawa Y
  • Journal Title: Respirology Volume: 17 Pages: 1048-59
  • Peer Reviewed
• [Presentation] Various effect of compensatory induction of PTEN wild against TGFβ-induced epithelial-mesenchymal transition (EMT) in epithelial cells (2012)
  • Author(s): Kusunose M, Hashimoto N, Kimura M, Hasegawa Y
  • Organizer: The FASEB Summer Research Conference
  • Place of Presentation: Saxtons River, USA
  • Year and Date: 20120722-27
• [Presentation] Compensatory induction of mutation of phosphorylation sites in PTEN inhibits hypoxia-induced epithelial-mesenchymal transition (EMT) in epithelial cells (2012)
  • Author(s): Kimura M, Hashimoto N, Kusunose M, Hasegawa Y
  • Organizer: The FASEB Summer Research Conference
  • Place of Presentation: Saxtons River, USA
  • Year and Date: 20120722-27
• [Presentation] Inhibition of TGFβ-induced phenotype alterations through epithelial-mesenchymal transition (EMT) in epithelial cells by gene mutation of phosphorylation sites in PTEN (2012)
  • Author(s): Hashimoto N, Kusunose M, Kimura M, Hasegawa Y
  • Organizer: The FASEB Summer Research Conference
  • Place of Presentation: Saxtons River, USA
  • Year and Date: 20120722-27
• [Presentation] Acute and persistent hypoxia differentially induces surfactant protein D modulation and epithelial-mesenchymal transition via hypoxia-inducible factor 1αand twist stimulation in acute lung injury/fibrosis (2012)
  • Author(s): Hashimoto N, Sakamoto K, Hasegawa Y
  • Organizer: The 2012 American Thoracic Society (ATS) International Conference
  • Place of Presentation: San Francisco, USA
  • Year and Date: 20120518-23
• [Presentation] Compensatory induction of mutated phosphorylation sites in the PTEN C-terminal suppresses tumor growth in lung cancers in vivo (2012)
  • Author(s): Hashimoto N, Aoyama D, Sakamoto K, Hasegawa Y
  • Organizer: The 2012 American Thoracic Society (ATS) International Conference
  • Place of Presentation: San Francisco, USA
  • Year and Date: 20120518-23