2015 Fiscal Year Final Research Report
Regulation of protease activities on the epithelial cell surface and its significance in epithelial disorders.
| Project/Area Number |
24390099
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | University of Miyazaki |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TAKEDA NAOKI 熊本大学, 生命資源研究支援センター, 助教 (90304998)
ISHIDA YOICHI 明治薬科大学, 薬学部, 講師 (90510454)
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| Co-Investigator(Renkei-kenkyūsha) |
KAWAGUCHI MAKIKO 宮崎大学, 医学部, 助教 (90405598)
FUKUSHIMA TSUYOSHI 宮崎大学, 医学部, 助教 (10452913)
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| Project Period (FY) |
2012-04-01 – 2016-03-31
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| Keywords | 病理学 / 実験病理学 / プロテアーゼ / プロテアーゼインヒビター / 上皮細胞 / 発癌 / 浸潤転移 / HAI-1 |
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| Outline of Final Research Achievements |
Membrane-associated protease inhibitors HAI-1 and -2 are important in regulating the pericellular serine protease activities of epithelial cells. This study aimed to analyze the roles for HAIs in normal homeostasis of epithelial cells and the effects of HAI insufficiency on cancer progression. We revealed that HAI-1 had suppressive roles in pericellular activations of HGF and PAR-2. HAI-1 was a suppressor of intestinal carcinogenesis and inhibited EMT, invasion, and metastasis of oral squamous cell carcinoma and pancreatic adenocarcinoma cells. Moreover, we found that HAI-1 maintained the assembly of keratin into desmosomes in keratinocytes by regulating PAR-2-dependent p38 signaling. Also, we have generated HAI-2floxed/floxed mouse that will be critically required for the development of the conditional HAI-1 knockout mouse. Those mice would accelerate the studies for in vivo functions of HAI-2.
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| Free Research Field |
医歯薬学
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