ハイホウ ジョウヒ サイボウ ニ オケル ミズチャンネル aquaporin-5 ノ イデンシ ハツゲン チョウセツ ニ カンスル ブンシ セイブツガク テキ ケンキュウ

The alveolar epithelium, which covers the internal surface of the lung, is composedof two highly specialized cell types, alveolar type I (ATI) cells and alveolar type II (ATII) cells. ATI damage is a major hallmark of many pulmonary diseases. Following injury, the alveolar epithelium is repaired by the proliferation and transdifferentiation of ATII cells into ATI cells. However, the mechanisms that underlie the regulation of the transdifferentiation of ATII cells into ATI cells have not yet been elucidated. In the distal lung, AQP5 is highly and selectively expressed in ATI cells, suggesting that AQP5 expression may be coordinately regulated with ATI cell differentiation. In addition, it has been reported that targeted deletion of AQP5 in mice results in a significant decrease in osmotic water permeability of the alveolar-capillary barrier in distal lung, suggesting that AQP5 in ATI cells plays an important role in maintaining water homeostasis in the lung. Previous studies revealed that AQP5 xpression is decreased at inflammatory region in many pulmonary diseases such as acute lung injury (ALI). Therefore, the pharmacological modulation of lung AQP5 expression may provide a novel approach to treat abnormal fluid clearance in ALI and pulmonary edema. In this study, the initial objective was to examine the molecular mechanisms underlying the ATI cell-specific expression of the AQP5 gene. The second objective was to examine the pharmacological modulation of AQP5 expression