MECHANISMS FOR CHRONIC UVR-INDUCED DAMAGE TO SKIN
紫外线引起的皮肤慢性损伤的机制
基本信息
- 批准号:2800596
- 负责人:
- 金额:$ 0.22万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1996
- 资助国家:美国
- 起止时间:1996-07-10 至 1999-06-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION: (Adapted from the applicant's abstract) - The long-term
objective of this research is to elucidate mechanisms responsible for the
dermal remodeling that occurs in response to exposure of skin to solar UV
radiation (UVR) over many years with the hope of devising strategies to
inhibit these tissue alterations. Age-related changes in skin (photoaging
and intrinsic aging) result in clinically important physiological changes
and are a significant medical problem in the elderly. The approach taken in
this proposal is to investigate the importance of mediators produced by
three cell types, keratinocytes, mast cells, and neutrophils in the
development of photoaged skin and particularly, in the increased synthesis
of tropoelastin and glycosaminoglycans (GAGs).
The first specific aim is to determine whether chronic exposure of skin to
UVR induces production of mediators from epidermal cells that initiate
dermal photoaging. This will be accomplished by: a) Determining whether
the epidermis is the primary site for absorption of UVR that initiates
changes in elastin, GAGs, histology and tropoelastin mRNA steady-state
levels. b) Assessing the ability of supernatants from keratinocytes that
are exposed to UVR in vitro to stimulate fibroblast synthesis of
tropoelastin and GAGs and increase tropoelastin steady state mRNA levels.
Possible UVR-induced mediators will be evaluated. The second specific aim
is to determine whether mast cell products are important mediators in the
mechanism for dermal photoaging. This will be accomplished by: a)
Comparing the elastin, GAGs, and histology produced by chronic UVR exposure
of mast cell-deficient mice and normal mice. b) Determining whether dermal
fibroblasts increase their synthetic activity in response to mast cell
products in vitro using mixtures from activated and degranulated mast cells
and selected mast cell products. Rates of synthesis of tropoelasin and
GAGs, and mRNA levels for tropoelastin will be measured. The third specific
aim is to test the hypothesis that products of neutrophils are important
mediators in the mechanism for dermal photoaging. Neutrophil
elastase-deficient mice will be employed, and synthesis of GAGs, character
of GAGs and histology will be used to measure the effects of chronic UV by
exposure. Neutrophil products will be tested in vitro for their ability to
alter fibroblast synthetic activity.
描述:(改编自申请人的摘要)-长期
这项研究的目的是阐明机制,负责
皮肤暴露于太阳紫外线后发生的皮肤重塑
辐射(UVR)多年来,希望制定战略,
抑制这些组织变化。 皮肤老化相关变化(光老化
和内在老化)导致临床上重要的生理变化
并且是老年人的重要医学问题。 所采取的做法
这一建议是为了调查调解人产生的重要性,
三种细胞类型,角质形成细胞,肥大细胞和中性粒细胞,
光老化皮肤的发展,特别是在增加的合成
原弹性蛋白和糖胺聚糖(GAG)。
第一个具体目标是确定皮肤长期暴露于
UVR诱导表皮细胞产生介质,
皮肤光老化 这将通过以下方式实现:a)确定是否
表皮是吸收UVR的主要部位,
弹性蛋白、GAG、组织学和弹性蛋白原mRNA稳态的变化
程度. B)评估来自角质形成细胞的上清液
在体外暴露于UVR以刺激成纤维细胞合成
在一些实施方案中,本发明的组合物可增加弹性蛋白原和GAG的表达,并增加弹性蛋白原稳态mRNA水平。
将评价可能的UVR诱导介质。 第二个具体目标
是为了确定肥大细胞产物是否是重要的介质,
皮肤光老化的机制。 这将通过以下方式实现:a)
比较慢性UVR暴露产生的弹性蛋白、GAG和组织学
肥大细胞缺陷小鼠和正常小鼠的比较。 B)确定皮肤
成纤维细胞响应肥大细胞增加其合成活性
使用来自活化和脱颗粒肥大细胞的混合物的体外产品
和精选的肥大细胞产品。 弹性蛋白原的合成速率,
将测量GAG和原弹性蛋白的mRNA水平。 第三特定
目的是检验中性粒细胞的产物是重要的假设,
皮肤光老化机制中的介质。 中性粒
将使用弹性蛋白酶缺陷小鼠,并将GAG的合成、特征
的GAG和组织学将用于测量慢性紫外线的影响,
exposure. 将在体外测试Neutrophil产品的能力,
改变成纤维细胞合成活性。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('IRENE KOCHEVAR', 18)}}的其他基金
MECHANISMS FOR CHRONIC UVR-INDUCED DAMAGE TO SKIN
紫外线引起的皮肤慢性损伤的机制
- 批准号:
2442850 - 财政年份:1996
- 资助金额:
$ 0.22万 - 项目类别:
MECHANISMS FOR CHRONIC UVR-INDUCED DAMAGE TO SKIN
紫外线引起的皮肤慢性损伤的机制
- 批准号:
6632628 - 财政年份:1996
- 资助金额:
$ 0.22万 - 项目类别:
MECHANISMS FOR CHRONIC UVR-INDUCED DAMAGE TO SKIN
紫外线引起的皮肤慢性损伤的机制
- 批准号:
2732880 - 财政年份:1996
- 资助金额:
$ 0.22万 - 项目类别:
MECHANISMS FOR CHRONIC UVR-INDUCED DAMAGE TO SKIN
紫外线引起的皮肤慢性损伤的机制
- 批准号:
6511871 - 财政年份:1996
- 资助金额:
$ 0.22万 - 项目类别:
MECHANISMS FOR CHRONIC UVR-INDUCED DAMAGE TO SKIN
紫外线引起的皮肤慢性损伤的机制
- 批准号:
2083651 - 财政年份:1996
- 资助金额:
$ 0.22万 - 项目类别:
MECHANISMS FOR CHRONIC UVR-INDUCED DAMAGE TO SKIN
紫外线引起的皮肤慢性损伤的机制
- 批准号:
6045349 - 财政年份:1996
- 资助金额:
$ 0.22万 - 项目类别:
MECHANISMS FOR CHRONIC UVR-INDUCED DAMAGE TO SKIN
紫外线引起的皮肤慢性损伤的机制
- 批准号:
6375020 - 财政年份:1996
- 资助金额:
$ 0.22万 - 项目类别:
MECHANISMS FOR CHRONIC UVR INDUCED DAMAGE TO SKIN
慢性紫外线对皮肤造成损害的机制
- 批准号:
2807300 - 财政年份:1996
- 资助金额:
$ 0.22万 - 项目类别:
ULTRAVIOLET LIGHT INDUCED PHENOMENA IN BIOMEMBRANES
生物膜中的紫外线诱导现象
- 批准号:
2175899 - 财政年份:1981
- 资助金额:
$ 0.22万 - 项目类别:
ULTRAVIOLET LIGHT INDUCED PHENOMENA IN BIOMEMBRANES
生物膜中的紫外线诱导现象
- 批准号:
3278615 - 财政年份:1981
- 资助金额:
$ 0.22万 - 项目类别:
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