Regulation of phenotype and gene expression in alveolar epithelial cells
| Project/Area Number |
12670201
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
SUZUKI Yasuhiro KYOTO UNIVERSITY Institute for Frontier Medical Sciences, 再生医科学研究所, 教授 (90027110)
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| Co-Investigator(Kenkyū-buntansha) |
HIRAYOSHI Kazunori KYOTO UNIVERSITY Institute for Frontier Medical Sciences, Dept. Ultrastructural Research, Instructor, 再生医科学研究所, 講師 (80199108)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | type II cell / transdifferentiation / sulfotransferase / proteoglycan / cell spreading / lung damage / MT-MMP / 肺傷害 / 肺胞上皮細胞 / 遺伝子発現 / ヘパラン硫酸 / ハービマイシンA / リチウム |
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| Research Abstract |
We investigated the expression of N-deacetylase/sulfotransferase (NDST) in rat type II epithelial cells in vitro and in vivo. Expression of NDST mRNA depended on cell density and matrix. It was induced when type II epithelial cells transdifferentiated to T1a-expressing type I cells and correlated with cell spreading. Anti-NDST antibody only slightly reacted to the epithelial cells in lungs from fetal rats at 16th day of pregnancy but no reaction was obtained in the lungs at later ages except Clara cells and type II cells in adult rats. In HCl-induced lung damage, atypical epithelial cells surrounding the lesion and those infiltrating into the lesion reacted to anti-PCNA antibody suggesting proliferating at day 2 of treatment. These cells highly expressed MT2- and 1-MMP. At days 7 and 14, many type II cells still invaded into the fibrotic lesion. NDST was remarkably expressed in these epithelial cells at day 2 and was in some cells in the newly formed alveoli until day 14. In vitro analysis revealed that herbimycin A induced expression of NDST mRNA and this induction was abolished by proteasome inhibitors. Lithium chloride inhibited both NDST expression and cell spreading. Sodium chlorate also inhibited cell spreading. In spreading cells, mRNA and complexed form of b-catenin increased and b-catenin was localized at the actin marginal band and outside of it.
These results suggest that NDST is involved rather in the repair of lung damage than in fetal lung morphogenesis and is expressed when type II cells spread and transdifferentiate into type I cells after migration, proliferation and infiltration into the lesion to form new alveoli and that b-catenin is one of the regulators of NDST expression, since the inhibitory factor for NDST expression is sensitive to proteasome and is induced by lithium chloride.
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Report
(3 results)
Research Products
(6 results)
