MATRILYSIN IN LUNG EPITHELIAL CELL INJURY AND REPAIR
基质溶素在肺上皮细胞损伤和修复中的作用
基本信息
- 批准号:6202222
- 负责人:
- 金额:$ 20.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1999
- 资助国家:美国
- 起止时间:1999-09-01 至 2000-08-31
- 项目状态:已结题
- 来源:
- 关键词:alveolar macrophages cell migration enzyme activity extracellular matrix proteins gene expression genetic regulatory element human tissue immunocytochemistry in situ hybridization inflammation laboratory mouse laboratory rat lung alveolus lung injury metalloendopeptidases proteolysis respiratory epithelium tissue /cell culture
项目摘要
We have observed the strong expression of the MMP matrilysin by alveolar
epithelial cells following alveolar injury associated with organizing
diffuse alveolar damage, post-bone marrow transplant idiopathic pneumonia
syndrome, and interstitial pneumonitis. Matrilysin is not found in the
respiratory epithelium of normal lung. Following lung surgery, matrilysin
was detected by immunohistochemistry and in situ hybridization in "row" of
type II cells marching across denuded alveolar walls. Matrilysin-positive
cells were found largely in areas of damaged or destroyed basement
membrane and rested on a fibronectin-containing matrix. Matrilysin is
frequently an "epithelial cell-derived" MMP, but other MMPs which are
known to be produced by some epithelial cells, namely collagenase-I,
stromelysin-1, and gelatinase B (MMP-9), were not produced by human lung
respiratory epithelium. In vitro studies of both rat and human alveolar
epithelial cells demonstrated strong capacity for matrilysin mRNA and
protein expression. Expression of matrilysin was also markedly induced in
airway epithelial cells in cystic fibrosis and severe asthma, again
suggesting a function in injury-mediated responses. Supporting this
concept, we found enhanced matrilysin expression by migrating human airway
(tracheal) epithelial cells in an ex vivo model of tissue repair. In such
explants, following mechanical wounding, immunoreactive matrilysin was
present both within and underneath the migrating tracheal epithelial
cells. Based upon these observations, we hypothesize that matrilysin
expression by type II pneumocytes accompanies severe alveolar injury, and
speculate that the proteolytic activity of this MMP is needed to
facilitate cell migration and repair. To address this hypothesis, we
propose the following specific aims: 1) we will examine the effect of
matrilysin expression by alveolar epithelial cells on alveolar repair
following experimental acute lung injury; 2) we will determine the effects
of matrilysin on human and rodent alveolar epithelial cell behavior in
vitro; and 3) we will define how matrilysin expression is regulated in
human and rodent alveolar epithelial cells. To accomplish these
objectives, we will employ diverse cell biological and molecular biologic
approaches including the study of matrilysin-deficient versus wild-type
mice. We will determine whether matrilysin is necessary for the migration
of type II pneumocytes, whether contact of cells with provisional matrix
proteins stimulates matrilysin expression, and the intracellular
mechanisms of matrilysin induction in alveolar epithelial cells.
我们观察到肺泡中MMP基质溶解素的强烈表达
项目成果
期刊论文数量(0)
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会议论文数量(0)
专利数量(0)
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HOWARD G WELGUS其他文献
HOWARD G WELGUS的其他文献
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{{ truncateString('HOWARD G WELGUS', 18)}}的其他基金
MATRILYSIN IN LUNG EPITHELIAL CELL INJURY AND REPAIR
基质溶素在肺上皮细胞损伤和修复中的作用
- 批准号:
6505082 - 财政年份:2001
- 资助金额:
$ 20.75万 - 项目类别:
MATRILYSIN IN LUNG EPITHELIAL CELL INJURY AND REPAIR
基质溶素在肺上皮细胞损伤和修复中的作用
- 批准号:
6347589 - 财政年份:2000
- 资助金额:
$ 20.75万 - 项目类别:
MATRILYSIN IN LUNG EPITHELIAL CELL INJURY AND REPAIR
基质溶素在肺上皮细胞损伤和修复中的作用
- 批准号:
6109689 - 财政年份:1998
- 资助金额:
$ 20.75万 - 项目类别:
EXPRESSION OF MATRIX METALLOPROTEINASES BY MONOCYTES AND ROLE IN LUNG BIOLOGY
单核细胞表达基质金属蛋白酶及其在肺生物学中的作用
- 批准号:
6241789 - 财政年份:1997
- 资助金额:
$ 20.75万 - 项目类别:
MATRIX METALLOPROTEINASES IN CUTANEOUS WOUND HEALING
基质金属蛋白酶在皮肤伤口愈合中的作用
- 批准号:
2079106 - 财政年份:1984
- 资助金额:
$ 20.75万 - 项目类别:
MATRIX METALLOPROTEINASES IN CUTANEOUS WOUND HEALING
基质金属蛋白酶在皮肤伤口愈合中的作用
- 批准号:
2079105 - 财政年份:1984
- 资助金额:
$ 20.75万 - 项目类别:
MATRIX METALLOPROTEINASES IN CUTANEOUS WOUND HEALING
基质金属蛋白酶在皮肤伤口愈合中的作用
- 批准号:
2769562 - 财政年份:1984
- 资助金额:
$ 20.75万 - 项目类别:
MATRIX METALLOPROTEINASES IN CUTANEOUS WOUND HEALING
基质金属蛋白酶在皮肤伤口愈合中的作用
- 批准号:
2517434 - 财政年份:1984
- 资助金额:
$ 20.75万 - 项目类别:
THE BIOLOGICAL ROLE OF HUMAN SKIN COLLAGENASE INHIBITOR
人类皮肤胶原酶抑制剂的生物学作用
- 批准号:
3157366 - 财政年份:1984
- 资助金额:
$ 20.75万 - 项目类别:
THE BIOLOGICAL ROLE OF HUMAN SKIN COLLANGENASE INHIBITOR
人类皮肤胶原酶抑制剂的生物学作用
- 批准号:
3071281 - 财政年份:1984
- 资助金额:
$ 20.75万 - 项目类别:
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