Project/Area Number |
18590844
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Respiratory organ internal medicine
|
Research Institution | Hamamatsu University School of Medicine |
Principal Investigator |
CHIDA Kingo Hamamatsu University School of Medicine, Department of Internal Medicine, second Division, Associate Professor (40197611)
|
Project Period (FY) |
2006 – 2007
|
Project Status |
Completed (Fiscal Year 2007)
|
Budget Amount *help |
¥3,390,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
|
Keywords | Epithelial mesenchvmat transition / Tracheal epithelial cells / TGF-β1 / matrix metalloproteinase |
Research Abstract |
Background: Epithelial mesenchymal transition (EMT) is known as the process by which differentiated epithelial cells undergo phenotypic transition to mesenchymal cells. Possibly, this process may occur in certain airway fibrotic diseases involving airway remodeling. Objectives: To clarify whether airway epithelial cells can differentiate mesenchymal cells through EMT. Methods: Mouse tracheal epithelial cells (mTEC) from BALB/c mouse were isolated, and cultured in an air-liquid interface (ALI) system in the presence or absence of TGF-p I. The expression of a-smooth muscle actin (a-SMA), vimentin, zonula occludens-I (Zo-I) and occludin was examined by immunofluorescence staining and westem blotting. Production of matrix metalloproteinase (MMP)-9 in culture medium was measured by enzyme linked immunosorbent assay. Results: Immunofluorescent staining revealed that TOF-p I treatment for 14 days induced the expression of mesenchymal markers, a-SMA and vimentin, and decreased the expression.of epithelial markers, Zo-1 and occluding in mTEC. Additionally, a-SMA and Zo-1 were colocalized within the single cells treated with TGF-(1l. In western blotting analysis, TGF-p1 treatment significantly enhanced the expression of a-SMA and vimentin, while it significantly reduced the expression of Zo-1 and occluding over time. Concentrations of MMP-9 in the culture medium were significantly higher in mTEC treated with TOF-β1 than those non-treated. Conclusions: These data suggest that EMT was induced by TGF-βl in the primary culture of mTEC with the ALI system, leading to the possibility that airway epithelial cells participates in airway remodeling through EMT.
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