Function of Fibulins

纤维蛋白的功能

• 批准号: 6757826
• 负责人: MON-LI H. CHU
• 金额: $ 29.85万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6757826
• 关键词: animal genetic material tag; cell type; coronary vessels; embryonic stem cell; extracellular matrix proteins; flow cytometry; gene expression; gene mutation; gene targeting; genetic markers; genetic promoter element; genetic regulatory element; genetically modified animals; green fluorescent proteins; growth /development; heart disorder; heart septum; immunocytochemistry; in situ hybridization; laboratory mouse; polymerase chain reaction; protein biosynthesis; protein structure function; southern blotting; tissue /cell culture

DESCRIPTION (applicant's description): The fibulins are an emerging family of extracellular matrix proteins characterized by the presence of tandem arrays of calcium-binding epidermal growth factor-like modules and a common C-terminal globular domain. Five members have been identified to date and they belong to two subgroups. The first two members, fibulin-1 and -2, are more related to each other by sequence identity and modular structure than to the three recently described members, fibulin-3, -4 and -5. All fibulins, except for fibulin-3, are highly abundant in the heart and blood vessel walls and thus may play essential roles in the cardiovascular system. Our laboratory first identified fibulin-2 and has subsequently studied fibulin-1 and -2 extensively. We and others have shown that fibulin- 1 and -2 are prominent components of heart septa and valves as well as aorta, pulmonary artery, and various large and small blood vessels. Fibulin-1 and -2 have also been shown to be present in the elastic fibers of the blood vessel walls where they colocalize with endostatin, the angiogenesis inhibitor. During embryonic development, fibulin-1 and -2 are highly specific markers for endocardial mesenchyme and smooth muscle cells of various types of blood vessels. The expression patterns of flbulin-1 and -2 overlap but there are distinct temporal and spatial differences. A critical role for fibulin-1 in blood vessel formation is demonstrated by our recent work showing that mice lacking fibulin- 1 are perinatally lethal as a result of massive bleeding. In this renewal application, we plan to continue studying the biological roles of fibulin-1 and fibulin-2 using biochemical approaches and transgenic mice generated by gene targeting, and to begin investigating the molecular mechanisms by which the cell-type specific expressions of fibulin genes are controlled. In addition, we propose to use flbulin-1 and -2 genes as markers to study in detail the development of heart septa and valves, great vessels and coronary blood vessels. The proposed studies will provide insights into the role of fibulins in human disease and the mechanism of cardiovascular development.

描述（申请人的描述）：纤维蛋白是一个新兴的家族 细胞外基质蛋白的特征是存在串联阵列 钙结合表皮生长因子样模块和共同的 C 末端 球状域。迄今为止，已确定五名成员的身份，他们分别属于 两个子组。前两个成员 fibulin-1 和 -2 与 通过序列同一性和模块结构彼此比三者 最近描述的成员 fibulin-3、-4 和 -5。所有纤维蛋白，除了 fibulin-3 在心脏和血管壁中含量很高，因此可能 在心血管系统中发挥重要作用。我们实验室首先 鉴定出 fibulin-2，随后广泛研究了 fibulin-1 和 -2。 我们和其他人已经证明 fibulin-1 和 -2 是 心脏隔膜和瓣膜以及主动脉、肺动脉和各种大动脉 和小血管。 Fibulin-1 和 -2 也被证明存在于 血管壁的弹性纤维与它们共定位 内皮抑素，血管生成抑制剂。在胚胎发育过程中，fibulin-1 和-2是心内膜间质和平滑肌的高度特异性标记物 各种血管的细胞。 flbulin-1的表达模式 和-2重叠，但存在明显的时间和空间差异。一个 我们的研究证明了 fibulin-1 在血管形成中的关键作用 最近的研究表明，缺乏 fibulin-1 的小鼠在围产期是致命的 大出血的结果。在此续签申请中，我们计划继续 利用生化研究 fibulin-1 和 fibulin-2 的生物学作用 方法和通过基因靶向产生的转基因小鼠，并开始 研究细胞类型特异性的分子机制 fibulin 基因的表达受到控制。此外，我们建议使用 flbulin-1和-2基因作为标记来详细研究心脏的发育 隔膜和瓣膜、大血管和冠状血管。拟议的 研究将深入了解纤维蛋白在人类疾病中的作用 心血管发育机制。

项目成果

Confocal laser scanning analysis of the association of fibulin-2 with fibrillin-1 and fibronectin define different stages of skin regeneration.

对 fibulin-2 与 fibrillin-1 和纤连蛋白关联的共聚焦激光扫描分析定义了皮肤再生的不同阶段。

• DOI: 10.1046/j.1523-1747.1999.00483.x
• 发表时间: 1999
• 期刊: The Journal of investigative dermatology
• 作者: Raghunath,M;Tschödrich-Rotter,M;Sasaki,T;Meuli,M;Chu,ML;Timpl,R
• 通讯作者: Timpl,R

Developmental changes in the basement membrane of the normal and hypothyroid postnatal rat testis: segmental localization of fibulin-2 and fibronectin.

正常和甲状腺功能减退的产后大鼠睾丸基底膜的发育变化：fibulin-2 和纤连蛋白的节段定位。

• DOI: 10.1095/biolreprod58.5.1123
• 发表时间: 1998
• 期刊: Biology of reproduction
• 影响因子: 3.6
• 作者: Loveland,K;Schlatt,S;Sasaki,T;Chu,ML;Timpl,R;Dziadek,M
• 通讯作者: Dziadek,M

Prominent expression of lysyl oxidase during mouse embryonic cardiovascular development.

赖氨酰氧化酶在小鼠胚胎心血管发育过程中的显着表达。

• DOI: 10.1002/ar.a.10002
• 发表时间: 2003
• 期刊: The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology.
• 作者: Tsuda,Takeshi;Pan,Te-Cheng;Evangelisti,Lucia;Chu,Mon-Li
• 通讯作者: Chu,Mon-Li

Fibulins in development and heritable disease.

• DOI: 10.1002/bdrc.20003
• 发表时间: 2004-03-01
• 期刊: Birth defects research. Part C, Embryo today : reviews
• 作者: Chu, Mon-Li;Tsuda, Takeshi
• 通讯作者: Tsuda, Takeshi