Preparation of homotrimer-gels composed of type I collagen α1 chain for novel biomaterials as drug-delivery.

由 I 型胶原 α1 链组成的同三聚体凝胶的制备，用于新型生物材料作为药物递送。

• 批准号: 15500314
• 负责人: HORI Hisae
• 金额: $ 2.43万
• 依托单位: Tokyo Medical and Dental University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15500314/
• 关键词: Collagen; in vitro translation; α1 chain; Homotrimer-gel; Drug delivery; Endostatin; Gelatin allergy

The drug-delivery systems using biomaterials are important research subjects in the field of pharmacology. The collagen obtained from bovine bone and skin, has been one of the most useful carrier biomaterials for this purpose by entrapping drugs in gel formation at body temperature and for a stabilizer in vaccine. Recently, it is suggested that contamination of pathogenic prion protein would be derived from bovine bone and that gelatin allergy was caused by bovine α2 chain of type I collagen. To develop nonallergenic and pathogen-free collagen, we investigated on preparation of novel homotrimer-gel composed of human type I collagen α1 chains {α1(I)_3} in recombinant technology, and the controlled release of drugs using the collagen-gel, focusing on a new drug delivery system (DDS) in this research project. Preparation of homotrimer-gel composed of {α1(I)_3} was examined using in vitro translation methods. The cloned human α1 chain cDNA (collagenous domain, 3.2 kbp) was inserted into vectors which were used pIVEX 2.3d for bacterial expression system and pIVEX 1.3WG for wheat germ expression system. Since recombinant α1 chain protein by both expression systems showed very low yield and recovered in insoluble fraction, it needed to search more effective expression system. In drug administration study using endostatin as antiangiogenic factor, the systemic administration of endostatin had an arthritis inhibiting effect in rheumatoid arthritis animal model. In the other administration study for tumor bearing mice, the injections of atelocollagen entrapped of antisence-oligonucleotides of omithine decarboxylase (ODC) which is known to be regulator of tumor growth, showed regression of tumor in the mice. These results suggested that collagen-gel entrapped of drugs was thought to be effective new DDS.

使用生物材料的药物传递系统是药理学领域的重要研究对象。从牛骨头和皮肤获得的胶原蛋白一直是为此目的而成为最有用的载体生物材料之一，它通过在体温下和疫苗中的稳定剂中的凝胶形成中捕获药物。最近，提出，致病性prion蛋白的污染将来自牛骨，明胶过敏是由I型胶原蛋白的牛α2链引起的。为了开发非过敏性和无病原体的胶原蛋白，我们研究了重组技术中由人类I胶原蛋白α1链{α1（i）_3}组成的新型同型聚物凝胶的准备，并使用胶原蛋白释放了药物，并使用胶原蛋白释放了这项研究项目（DDS）（DDS）。使用体外翻译方法检查了由{α1（i）_3}组成的同构凝胶的制备。将克隆的人α1链cDNA（胶原结构域，3.2 kbp）插入载体中，该向量用于细菌表达系统的Pivex 2.3d，而Pivex 1.3WG用于小麦生殖表达系统。由于两种表达系统的重组α1链蛋白都表现出非常低的产率并以不溶性分数恢复，因此它需要搜索更有效的表达系统。在药物管理的研究中，使用内接抑素作为抗血管生成因子，内抑素的全身给药对类风湿关节炎动物模型具有抑制作用。在另一项针对肿瘤轴承小鼠的管理研究中，注射了邻苯二甲酸酯（Omithine decarpasylase）抗异源 - 寡核苷酸（ODC）的注射，已知是肿瘤生长的调节剂，显示出小鼠肿瘤的消退。这些结果表明，被认为是有效的新DD的胶原蛋白凝胶被认为是有效的。

项目成果

An analysis of the functional mechanisms of endostatin. -The anti-angiogenic activity of endostatin is mediated by its multiple binding ability.

内皮抑素的作用机制分析。

• 发表时间: 2004
• 期刊: Connective Tissue 36
• 作者: Yamaguchi;N.
• 通讯作者: N.

Omithine decarboxylase, mitogen-activated protein kinase and matrix metalloproteinase-2 expressions in human colon tumors.

鸟氨酸脱羧酶、丝裂原激活蛋白激酶和基质金属蛋白酶-2 在人结肠肿瘤中的表达。

• 期刊: World J.Gastroenterology (in press)
• 作者: Nemoto T.;Kubota;S.
• 通讯作者: S.

Identification and functional analysis of a caveolin-3 mutation associated with familial hypertrophic cardiomyopa

与家族性肥厚型心肌病相关的 Caveolin-3 突变的鉴定和功能分析

• 发表时间: 2004
• 期刊: Biochem.Biophys.Res.Comm. 313
• 作者: Hayashi T.;Arimura T.;Ueda T.;Shibata H.;Hohda S.;Takahashi T.;Hori H;Koga Y.;Oka N.;Imaizumi T.Yasunami M.;Kimura A.
• 通讯作者: Kimura A.

Spontaneous muscular dystrophy caused by a retrotransposal insertion in the mouse laminin alpha2 chain gene.

由小鼠层粘连蛋白 α2 链基因中的逆转录转座插入引起的自发性肌营养不良症。

• 发表时间: 2003
• 期刊: Neuromuscul Disord. 13
• 作者: Besse;S.
• 通讯作者: S.

Arthritis-inhibiting effect of systemic administration of endostatin in passive marine collagen-induced arthritis.

全身施用内皮抑素对被动海洋胶原诱导的关节炎的关节炎抑制作用。

• 发表时间: 2003
• 期刊: Ann.Rheum.Dis 62
• 作者: Kurosaka;D.Yoshida K;Yasuda J;Yokoyama T;Kingetsu I;Yamaguchi N;Joh K;Matsushima M;Saito S;Yamada A.
• 通讯作者: Yamada A.