2004 Fiscal Year Final Research Report Summary
Functional analysis of connective tissue factors involved in the epithlial remodeling of the digestive tract
| Project/Area Number |
14570025
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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 |
General anatomy (including Histology/Embryology)
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| Research Institution | Nippon Medical School (2004)
Dokkyo Medical University (2002-2003) |
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Principal Investigator |
OKA Atuko Nippon Medical School, Department of Biology, Professor, 医学部, 教授 (50175254)
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| Project Period (FY) |
2002 – 2004
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| Keywords | digestive tract / organ remodeling / thyroid hormone / tissue interaction / apoptosis / stem cell / organ culture / electroporation |
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| Research Abstract |
In the digestive tract during amphibian metamorphosis, under the control of the connective tissue, the larval epithelium undergoes apoptosis, whereas a small number of stem cells actively proliferate and form the adult epithelium similar to the mammalian counterpart. We previously examined expression profiles of thyroid hormone(TH) response genes and found that the connective tissue-specific expression of stromelysis-3 (ST3;MMP11) correlates well with the epithelial apoptosis, whereas that of BMP-4 correlates with development of the adult epithelium in the Xenopus laevis intestine. In this study, to clarify molecular mechanisms of the intestinal remodeling, we focused on functions of these TH response genes. First, using transgenic tadpoles expressing ST3 under the control of a heat shock-inducible promoter, we have shown by electron microscopy that the overexpression of ST3 induces apoptosis of the intestinal epithelium possibly through the modification of its basal lamina. Next, we performed organ culture experiments with BMP-4 and its antagonist, Chordin, proteins and have shown that BMP-4 causes precocious differentiation of the adult intestinal epithelium and inhibits cell proliferation of the connective tissue. Finally, to analyze functions of TH response genes more precisely, we established an in vitro gene transfer system by combining electroporation with organ culture techniques. Using this system, we overexpressed one of TH response genes, TH/bZip, in the epithelium of Xenopus tadpole intestines and demonstrated that TH/bZip functions as a growth activator during the intestinal remodeling. This in vitro system may provide a powerful tool for clarifying molecular mechanisms underlying the intestinal remodeling.
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[Book] Regulation of apoptosis by extracellular matrix during postembryonic development in Xenopus laevis. In : When cells die? : a comprehensive evaluation of apoptosis and programmed cell death. (Eds. Lockshin, R.A., Zakeri, Z.)2004
Author(s)
Ishizuya-Oka, A., Amano, T., Fu, L., Shi, Y.-B.
Total Pages
123-141
Publisher
John Wiley & Sons
Description
「研究成果報告書概要(和文)」より
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[Book] Regulation of apoptosis by extracellular matrix during postembryonic development m Xenopus laevis. In When Cells Die? : a comprehensive evaluation of apoptosis and programmed cell death. (Eds.Lockshin, R.A., Zakeri, Z.)2004
Author(s)
Ishizuya-Oka, A., Amano, T., Fu, Land Shi, Y.-B.
Total Pages
123-141
Publisher
John Wiley & Sons, New Jersey
Description
「研究成果報告書概要(欧文)」より
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