Molecular Target of Regenerative Pulmonary Medicine for Chronic Obstructive Pulmonary Disease

慢性阻塞性肺疾病再生肺医学的分子靶点

• 批准号: 23659431
• 负责人: HASEGAWA Yoshinori
• 金额: $ 2.33万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23659431/
• 关键词: 肺の再生; 低酸素; PTEN; 組織微小環境; 上皮間葉系移行; EMT; 肺構成細胞; 再生医療; 肺傷害

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.

为积累肺组织再生的基础研究成果，本研究对上皮-间充质转化（EMT）及其逆转现象（MET）进行了分子生物学研究。一个是扭曲，另一个是长期组织缺氧对EMT的影响。我们发现，持续缺氧诱导从头扭曲的表达，造成镇压SP-D和收购的EMT表型。三是组织微环境（TM）。在TM中，多种由PTEN负调控的信号通路被激活。然而，持续缺氧是否会影响PTEN活性仍然是一个谜。在本研究中，持续缺氧引起肺细胞中PTEN表达的降低和p-PTEN/PTEN比值的增加。这些结果表明，长期的组织缺氧和EMT的调节可能是重要的肺组织再生。

项目成果

Various effect of compensatory induction of PTEN wild against TGFβ-induced epithelial-mesenchymal transition (EMT) in epithelial cells

PTEN 野生代偿性诱导对 TGFβ 诱导的上皮细胞上皮间质转化 (EMT) 的各种影响

• 发表时间: 2012
• 作者: Kusunose M;Hashimoto N;Kimura M;Hasegawa Y
• 通讯作者: Hasegawa Y

Compensatory induction of mutation of phosphorylation sites in PTEN inhibits hypoxia-induced epithelial-mesenchymal transition (EMT) in epithelial cells

PTEN 磷酸化位点突变的代偿性诱导抑制上皮细胞缺氧诱导的上皮间质转化（EMT）

• 发表时间: 2012
• 作者: Kimura M;Hashimoto N;Kusunose M;Hasegawa Y
• 通讯作者: Hasegawa Y

Inhibition of TGFβ-induced phenotype alterations through epithelial-mesenchymal transition (EMT) in epithelial cells by gene mutation of phosphorylation sites in PTEN

通过 PTEN 磷酸化位点的基因突变抑制上皮细胞中 TGFβ 通过上皮-间质转化 (EMT) 诱导的表型改变

• 发表时间: 2012
• 作者: Hashimoto N;Kusunose M;Kimura M;Hasegawa Y
• 通讯作者: Hasegawa Y

Inhibition Of TGF-Beta-InducedPhenotype Alterations ThroughEpithelial-MesenchymalTransition(EMT) In Lung Cancer By GeneModulation Of Phosphorylations SitesIn Tumor Suppressor Pten

通过肿瘤抑制因子 Pten 磷酸化位点的基因调节抑制肺癌中 TGF-β 诱导的上皮间质转化 (EMT) 表型改变

• 发表时间: 2011
• 作者: Aoyama D;Hasegawa Y;et al.(7人7番目)
• 通讯作者: et al.(7人7番目)

Acute and persistent hypoxia differentially induces surfactant protein D modulation and epithelial-mesenchymal transition via hypoxia-inducible factor 1α and twist stimulation in acute lung injury/fibrosis

急性和持续缺氧通过缺氧诱导因子 1α 和扭转刺激在急性肺损伤/纤维化中差异诱导表面活性蛋白 D 调节和上皮间质转化

• 发表时间: 2012
• 作者: Suzuki Y;Suda T et al;Naozumi Hashimoto
• 通讯作者: Naozumi Hashimoto