MODEL FOR EPITHELIAL/BASEMENT MEMBRANE INTERACTIONS

上皮/基底膜相互作用模型

基本信息

项目摘要

Basic errors in the structure and function of extracellular matrix (or its specialized form basement membrane) leads to a broad spectrum of problems related to developmental abnormalities and secondary complications in such diseases as diabetes mellitus where basement membrane thickening and dysfunction is observed. Our understanding of the cellula mechanisms underlying normal and abnormal basement membrane formation and the role of matrix components in signal transmission during development has been limited by a lack of appropriate in vitro and in vivo models to experimental approach these problems. In order to better approach these problems, we have developed an in vivo cellular model in which basement membrane formation can be experimentally induced between an epithelial bilayer and its formation related to 1) the process of cytodifferentiation and morphogenesis and 2) disease processes which lead to abnormalities in the structure and function of basement membranes. This model has been developed from the invertebrate, Hydra vulgaris which is structurally reduced to an epithelial bilayer with an intervening basement membrane (mesoglea). Building on previously published studies, we have defined experimental conditions in which 1) pellets generated from cells isolated from adult Hydra form an epithelial bilayer, deposit an intervening basement membrane, and subsequently reform an adult Hydra structure within 72-96 hr through the processes of cytodifferentiation and morphogenesis and 2) as related to the disease diabetes mellitus, development of this cell-aggregation-morphogenesis system in the presence of elevated glucose levels leads to an abnormal thickening of basement membrane within 72-96 hr time frame as opposed to months or years as required in mammalian animal model of diabetes. Utilizing this in vivo epithelial/basement membrane model system we propose to test hypotheses directed at the cellular mechanisms involved in the normal and abnormal development of basement membrane and the concomitant transmission of epithelial signal which are involved in tissue cytodifferentiation and morphogenesis. Using a combination of cellular and molecular biology approaches we propose to focus on the following specific aims in order to further develop this nonmammalian in vivo model for application to biomedical research: 1. To examine the process of normal basement membrane formation during development and determine the precise role of basement membrane protein domains in tissue cytodifferentiation and morphogenesis. 2. To examine cellular mechanisms by which elevated glucose levels lead to an abnormal thickening of basement membrane as observed in individuals with diabetes mellitus.
细胞外基质(或其 特殊形式的基底膜)导致广泛的问题 与发育异常和继发性并发症有关, 糖尿病等疾病,基底膜增厚, 观察到功能障碍。我们对细胞机制的理解 正常和异常基底膜形成的基础和作用 在开发过程中, 由于缺乏适当的体外和体内模型, 实验方法解决这些问题。为了更好地接近这些 问题,我们已经开发了一种体内细胞模型,其中基底 膜形成可以通过实验在上皮细胞之间诱导, 双层及其形成与1)细胞分化过程有关 和形态发生,以及2)导致异常的疾病过程, 基底膜的结构和功能。该模型 由无脊椎动物水螅进化而来, 退化为上皮双层,其间有基底膜 (mesoglea)。基于先前发表的研究,我们定义了 实验条件,其中1)从分离的细胞产生的沉淀 从成年水螅形成上皮双层,存款, 基底膜,随后改革一个成年水螅结构内 72-96小时通过细胞分化和形态发生的过程, 2)与糖尿病有关, 高浓度葡萄糖下的细胞聚集-形态发生系统 在72-96小时内导致基底膜异常增厚 与哺乳动物所需的数月或数年相反的时间范围 糖尿病模型利用这种体内上皮/基底膜 模型系统,我们建议测试假设针对细胞 基底正常和异常发育的机制 膜和上皮细胞信号的伴随传输, 参与组织细胞分化和形态发生。使用 结合细胞和分子生物学方法,我们提出, 重点关注以下具体目标,以进一步发展这一点 用于生物医学研究的非哺乳动物体内模型:1.到 检查正常基底膜形成的过程, 开发和确定基底膜蛋白的确切作用 组织细胞分化和形态发生的结构域。2.审查 葡萄糖水平升高导致异常的 糖尿病患者基底膜增厚 糖尿病。

项目成果

期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Cell-extracellular matrix interactions under in vivo conditions during interstitial cell migration in Hydra vulgaris.
寻常水螅间质细胞迁移过程中体内条件下细胞与细胞外基质的相互作用。
Extracellular matrix (mesoglea) of Hydra vulgaris. II. Influence of collagen and proteoglycan components on head regeneration.
寻常水螅的细胞外基质(mesoglea)。
  • DOI:
    10.1016/0012-1606(91)90267-7
  • 发表时间:
    1991
  • 期刊:
  • 影响因子:
    2.7
  • 作者:
    SarrasJr,MP;Meador,D;Zhang,XM
  • 通讯作者:
    Zhang,XM
High molecular weight secretory products of the human pancreatic ductal epithelium and the effect of secretin on their discharge.
人胰腺导管上皮的高分子量分泌产物以及促胰液素对其分泌的影响。
  • DOI:
    10.1097/00006676-199203000-00002
  • 发表时间:
    1992
  • 期刊:
  • 影响因子:
    2.9
  • 作者:
    SarrasJr,MP;Huff,JK;Palmiter-Thomas,P
  • 通讯作者:
    Palmiter-Thomas,P
Evidence for cell surface extracellular matrix binding proteins in Hydra vulgaris.
普通水螅细胞表面细胞外基质结合蛋白的证据。
  • DOI:
    10.3109/15419069409014202
  • 发表时间:
    1994
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Agbas,A;SarrasJr,MP
  • 通讯作者:
    SarrasJr,MP
Hydra cell aggregate development is blocked by selective fragments of fibronectin and type IV collagen.
水螅细胞聚集体的发育被纤连蛋白和 IV 型胶原蛋白的选择性片段阻断。
  • DOI:
    10.1006/dbio.1994.1176
  • 发表时间:
    1994
  • 期刊:
  • 影响因子:
    2.7
  • 作者:
    Zhang,X;Hudson,BG;SarrasJr,MP
  • 通讯作者:
    SarrasJr,MP
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MICHAEL Peter SARRAS其他文献

MICHAEL Peter SARRAS的其他文献

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{{ truncateString('MICHAEL Peter SARRAS', 18)}}的其他基金

Developing and Improving Institutional Animal Resources at Rosalind Franklin Un.
罗莎琳德·富兰克林大学开发和改善机构动物资源。
  • 批准号:
    7628240
  • 财政年份:
    2009
  • 资助金额:
    $ 18.59万
  • 项目类别:
Use of Zebrafish as a Model for Diabetic Nephropathy
使用斑马鱼作为糖尿病肾病模型
  • 批准号:
    6459153
  • 财政年份:
    2002
  • 资助金额:
    $ 18.59万
  • 项目类别:
Use of Zebrafish as a Model for Diabetic Nephropathy
使用斑马鱼作为糖尿病肾病模型
  • 批准号:
    6622910
  • 财政年份:
    2002
  • 资助金额:
    $ 18.59万
  • 项目类别:
MODEL FOR GLUCOSE INDUCED BASEMENT MEMBRANE THICKENING
葡萄糖引起的基底膜增厚模型
  • 批准号:
    2147717
  • 财政年份:
    1995
  • 资助金额:
    $ 18.59万
  • 项目类别:
MODEL FOR GLUCOSE INDUCED BASEMENT MEMBRANE THICKENING
葡萄糖引起的基底膜增厚模型
  • 批准号:
    2734150
  • 财政年份:
    1995
  • 资助金额:
    $ 18.59万
  • 项目类别:
MODEL FOR GLUCOSE INDUCED BASEMENT MEMBRANE THICKENING
葡萄糖引起的基底膜增厚模型
  • 批准号:
    2147718
  • 财政年份:
    1995
  • 资助金额:
    $ 18.59万
  • 项目类别:
MODEL FOR GLUCOSE INDUCED BASEMENT MEMBRANE THICKENING
葡萄糖引起的基底膜增厚模型
  • 批准号:
    2444097
  • 财政年份:
    1995
  • 资助金额:
    $ 18.59万
  • 项目类别:
A MODEL FOR BASEMENT MEMBRANE THICKENING IN DIABETES
糖尿病基底膜增厚的模型
  • 批准号:
    3426184
  • 财政年份:
    1991
  • 资助金额:
    $ 18.59万
  • 项目类别:
MODEL FOR EPITHELIAL/BASEMENT MEMBRANE INTERACTIONS
上皮/基底膜相互作用模型
  • 批准号:
    3421551
  • 财政年份:
    1990
  • 资助金额:
    $ 18.59万
  • 项目类别:
MODEL FOR EPITHELIAL/BASEMENT MEMBRANE INTERACTIONS
上皮/基底膜相互作用模型
  • 批准号:
    3421548
  • 财政年份:
    1990
  • 资助金额:
    $ 18.59万
  • 项目类别:

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Investigating the molecular basis of basement membrane specialisation and basal surface organisation during epithelial tissue development
研究上皮组织发育过程中基底膜特化和基底表面组织的分子基础
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Understanding the Mechanisms and Consequences of Basement Membrane Aging in Vivo
了解体内基底膜老化的机制和后果
  • 批准号:
    10465010
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    2023
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  • 项目类别:
Mechanisms of epithelial migration and basement membrane assembly
上皮迁移和基底膜组装的机制
  • 批准号:
    10552458
  • 财政年份:
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A Comprehensive Endogenous Basement Membrane Toolkit to Elucidate how Basement Membranes Stretch on Mechanically Active Tissues and Decline during Aging
一个全面的内源性基底膜工具包,用于阐明基底膜如何在机械活动组织上伸展和衰老过程中的衰退
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果蝇中肠的基底膜修复动力学
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  • 资助金额:
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Basement membrane repair dynamics in the Drosophila midgut
果蝇中肠的基底膜修复动力学
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基底膜大分子的环境控制力学与组装
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衰老相关的基底膜胶原蛋白损失如何调节表皮屏障稳态
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