Reconstruction of basement membranes aiming at artificial organs
针对人工器官的基底膜重建
基本信息
- 批准号:10557113
- 负责人:
- 金额:$ 8.26万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B).
- 财政年份:1998
- 资助国家:日本
- 起止时间:1998 至 2000
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
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.
研究项目的最终目标是使人造器官在上皮层和细胞外基质之间插入基底膜材料。为了在体外制作IV型胶原分子,我们进行了以下研究:*平滑肌细胞下基底膜的分子组成在不同的器官中有所不同,这可能与单个器官的特定功能有关。卵泡地下膜中六种IV胶原蛋白基因的组织特异性表达。*分子形式的胶原蛋白IV在发育中不同。尽管犬Alport病例的肾脏中α5的mRNA表达水平降低,但α6的mRNA表达水平降低,但α6的mRNA表达水平却没有变化。但是两种链的蛋白质水平都找不到。这些结果表明,详细分析了上皮地下膜中胶原蛋白IV基因的分子形式的差异表达的可能性。血管生成和肿瘤生长。这些NCI结构域被证明可以调节内皮细胞粘附和通过不同的αV和β1整合素依赖性机制的迁移。此外,LMX1B专门与小鼠/人Col4a4内含子1中的假定增强剂结合,并上调包含增强子样序列的记者构建体。
项目成果
期刊论文数量(62)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Petitclerc E, Boutaud A, Prestayko A, Xu J, Sado Y, Ninomiya Y, Sarras MP Jr, Hudson BG, Brooks PC.: "New Functions for Non-collagenous Domains of Human Collagen Type IV.Novel integrin ligands inhibiting angiogenesis and tumor growth in vivo."J Biol Chem.
Petitclerc E、Boutaud A、Prestayko A、Xu J、Sado Y、Ninomiya Y、Sarras MP Jr、Hudson BG、Brooks PC.:“人类 IV 型胶原蛋白非胶原域的新功能。新型整合素配体抑制血管生成和肿瘤
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Nakano S. et al: "Differential tissular expression and localinzation 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 Investigations. 79. 281-292 (1999)
Nakano S. 等人:“正常乳腺、良性和恶性肿瘤中 IV 型胶原 α1(IV)、α2(IV)、α5(IV) 和 α6(IV) 链及其 mRNA 的差异组织表达和定位。”实验室研究. 79. 281-292 (1999)
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Lee G E et al.: "New form of X-linked dominant hereditary nephritis in dogs"Am. J. Vet. Res... 60. 373-383 (1999)
Lee G E 等人:“犬 X 连锁显性遗传性肾炎的新形式”Am。
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Petitclere E. et al.: "New Functions for non-collagenous domains of human collagen type IV. Novel integrin ligands inhibiting angiogenesis and tumor growth in vivo."J.Biochem.Chem.. 275. 8051-8061 (2000)
Petitclere E.等人:“人类 IV 型胶原蛋白非胶原蛋白结构域的新功能。新型整合素配体抑制体内血管生成和肿瘤生长。”J.Biochem.Chem.. 275. 8051-8061 (2000)
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- 影响因子:0
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Sado Y.et al.: "Induction of anti-GBM nephritisin rats by recombinant α_3(IV) and α_4(IV) NCl of typeIV collagen." Kidney International. 53. 664-671 (1998)
Sado Y. 等人:“通过 IV 型胶原的重组 α_3(IV) 和 α_4(IV) NCl 诱导抗 GBM 肾炎大鼠”,53. 664-671 (1998)。
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- 影响因子:0
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NINOMIYA Yoshifumi的其他基金
Anti tumor effect of micro RNA transferred by active targeting liposomes
主动靶向脂质体转移微小RNA的抗肿瘤作用
- 批准号:2465959024659590
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- 资助金额:$ 8.26万$ 8.26万
- 项目类别:Grant-in-Aid for Challenging Exploratory ResearchGrant-in-Aid for Challenging Exploratory Research
Development of Imaging Diagnosis for Lymphedema
淋巴水肿影像诊断的进展
- 批准号:2265932322659323
- 财政年份:2010
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- 项目类别:Grant-in-Aid for Challenging Exploratory ResearchGrant-in-Aid for Challenging Exploratory Research
Function of newly identified basal lamina structure fractone and regulation of neural stem cell differentiation at subventricular zone
新发现的基底层结构fractone的功能及其对室下区神经干细胞分化的调节
- 批准号:1639004816390048
- 财政年份:2004
- 资助金额:$ 8.26万$ 8.26万
- 项目类别:Grant-in-Aid for Scientific Research (B)Grant-in-Aid for Scientific Research (B)
Function of subendothelial basement membranes in Blood-Brain Barrier
内皮下基底膜在血脑屏障中的功能
- 批准号:1437043414370434
- 财政年份:2002
- 资助金额:$ 8.26万$ 8.26万
- 项目类别:Grant-in-Aid for Scientific Research (B)Grant-in-Aid for Scientific Research (B)
Functional Analysis of Basement Membrane Collagen Genes
基底膜胶原基因的功能分析
- 批准号:1169428011694280
- 财政年份:1999
- 资助金额:$ 8.26万$ 8.26万
- 项目类别:Grant-in-Aid for Scientific Research (B)Grant-in-Aid for Scientific Research (B)
Inhibitory mechanism of vascular endothelial cell proliferation by endostatin
内皮抑素抑制血管内皮细胞增殖的机制
- 批准号:1147027411470274
- 财政年份:1999
- 资助金额:$ 8.26万$ 8.26万
- 项目类别:Grant-in-Aid for Scientific Research (B)Grant-in-Aid for Scientific Research (B)
Functional Analysis of Collagen IV by Gene Targeting
通过基因打靶对 IV 型胶原蛋白进行功能分析
- 批准号:0904430809044308
- 财政年份:1997
- 资助金额:$ 8.26万$ 8.26万
- 项目类别:Grant-in-Aid for international Scientific ResearchGrant-in-Aid for international Scientific Research
Supramolecular Assembly and Function of New Basement Membrane Collagen Molecules
新型基底膜胶原分子的超分子组装及其功能
- 批准号:0845715408457154
- 财政年份:1996
- 资助金额:$ 8.26万$ 8.26万
- 项目类别:Grant-in-Aid for Scientific Research (B)Grant-in-Aid for Scientific Research (B)
Biological function of basement membrane
基底膜的生物学功能
- 批准号:0704426807044268
- 财政年份:1995
- 资助金额:$ 8.26万$ 8.26万
- 项目类别:Grant-in-Aid for international Scientific ResearchGrant-in-Aid for international Scientific Research
Biological Function of Type VIII Collagen
VIII 型胶原蛋白的生物学功能
- 批准号:0604415406044154
- 财政年份:1994
- 资助金额:$ 8.26万$ 8.26万
- 项目类别:Grant-in-Aid for international Scientific ResearchGrant-in-Aid for international Scientific Research
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