2000 Fiscal Year Final Research Report Summary
Reconstruction of basement membranes aiming at artificial organs
| Project/Area Number |
10557113
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
General surgery
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
NINOMIYA Yoshifumi Okayama University, Medical School, Professor, 医学部, 教授 (70126241)
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| Co-Investigator(Kenkyū-buntansha) |
YONEZAWA Tomoko Okayama University Medical School, Assistant, 医学部, 助手 (30304299)
MOMOTA Ryusuke Okayama University, Medical School, Assistant, 医学部, 助手 (80263557)
OOHASHI Toshitaka Okayama University, Medical School, Lecturer, 医学部, 講師 (50194262)
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| Project Period (FY) |
1998 – 2000
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| Keywords | basement membrane / collagen / tissue engineering / gene expression |
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| Research Abstract |
Ultimate goal of the research project is to make artificial organs to insert basement membrane materials between epithelial layers and extracellular matrix. In order to make type IV collagen molecules in vitro, we we did the following investigations :
* Molecular composition of basement membranes underneath smooth muscle cells varies in different organs, which could be related to specific function of the individual organs.
* We first isolated and characterized genomic DNA fragments that cover the 5'flanking sequences of COL4A3 and COL4A4 genes, which provided information to delineate the promoter activity for the tissue-specific expression of the six type IV collagen genes.
* Molecular forms of collagen IV in follicle basement membranes are different in development.
* We identified interactions between the α2(IV) and ProMMP-9 by immunoprecipitations and blotting.
* Basement membrane collagen IV molecules diminish in parallel with malignancy and invasiveness when analyzed in tumor progression.
* Although mRNA expression level of α5 decreased in kidney of a canine Alport case, that of α6 resulted in unchanged. But the protein level of both chains cannot be found any. These results suggest a possibility of a molecular form of α5/α6.
* Differential expression of collagen IV genes in epithelial basement membranes was analyzed in detail.
* Here we define a novel function for soluble non-collagenous (NC1) domains of the α2(IV), α3(IV), and α6(IV) chains of human collagen type IV in the regulation of angiogenesis and tumor growth. These NCI domains were shown to regulate endothelial cell adhesion and migration by distinct αv and β1 integrin-dependent mechanisms.
* In Lmx1b(-/-) mice, expression of both α3 and α4 is strongly diminished in GBM, whereas that of α1, α2 and α5 is unchanged. Moreover, LMX1B binds specifically to a putative enhancer in intron 1 of mouse/human COL4A4 and upregulates reporter constructs containing the enhancer-like sequence.
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[Publications] Momota, R., Sugimoto, M., Oohashi, T., Kigasawa, K., Yoshioka, H., and Ninomiya, Y.: "Two genes, COL4A3 and COL4A4 coding for the human α3(IV) and α4(IV) collagen chains are arranged head-to-head on chromosome 2q36."FEBS Letters. 424. 11-16 (1998)
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[Publications] Nakano S, Iyama K-I, Ogawa M, Tsuruta J, Yoshioka H, Sado Y, Oohashi T, and Ninomiya Y: "Differential Tissular Expression and Localization of Type IV Collagen α1(IV), α2(IV), α5(IV) and α6(IV) Chains and their mRNAs in Normal Breast, Benign and Malignant Tumors."Laboratory Investigation. 79. 281-292 (1999)
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「研究成果報告書概要(欧文)」より
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