Molecular Target of Regenerative Pulmonary Medicine for Chronic Obstructive Pulmonary Disease

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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.