The exploration of new therapeutic target and the investigation of the role of maintaining alveolar-epithelium cell integrity in acute respiratory distress syndrome

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670419
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: University of Miyazaki
• Principal Investigator: Nakazato Masamitsu 宮崎大学, 医学部, 教授 (10180267)
• Co-Investigator(Kenkyū-buntansha): Tsubouchi Hironobu 宮崎大学, 医学部, 助教 (60573988) ; Matsumoto Nobuhiro 宮崎大学, 医学部, 助教 (70418838) ; Miura Ayako 宮崎大学, 医学部 (70710903)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 上皮統合性 / 肺損傷 / 急性呼吸窮迫症候群 / タイトジャンクション / リモデリング / グレリン / Ｐｔｅｎ / 基底膜

Outline of Final Research Achievements

The pathological features of acute respiratory distress syndrome (ARDS) include injuries of alveolar epithelial cells (AECs) and destruction of the alveolar capillary barrier, which cause subsequent devastating lung fibrosis. Pten, a tumor suppressor gene, negatively regulates the PI3K/AKT pathway. To clarify the biological role of Pten in AEC in the pathogenesis of lung fibrosis, we used a AEC-specific null mutation of Pten mice (SOPten⊿/⊿). SOPten⊿/⊿ mice showed excessive lung fibrosis compared with the control after bleomycin administration. The expression of epithelial-mesenchymal transition (EMT) related molecules and the number of epithelial derived myofibroblasts were increased in the lungs of bleomycin-treated SOPten⊿/⊿ mice. Systemic administration of the Akt inhibitor ameliorated the BLM-induced lung injury. Our results indicate that Pten has the essential role in AEC integrity and they highlight the Pten/Akt pathway as a potential therapeutic target in ARDS.

Free Research Field

神経内分泌