THE ROLE OF LAMININ 5 IN DIABETIC ULCER HEALING
THE ROLE OF LAMININ 5 IN DIABETIC ULCER HEALING
批准号:
6789928
负责人:
JOHN Everett OLERUD
金额:
$49.75万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2000
资助国家:
美国
项目状态:
已结题
起止时间:
2000-09-30 至 2006-08-31
关键词:
中文摘要
说明(改编自应用程序)
2000年健康人大会的目标之一就是减少
糖尿病患者的下肢截肢率自1988年基线比率
到2000年,目标发病率为4.9/1000。尽管做出了努力
为了预防,截肢率在#年继续上升。
糖尿病患者。加深对糖尿病溃疡发病机制的认识
需要新的治疗策略来扭转这一上升趋势。
截肢率。这个应用的目标是使用新的分子
通过增加移行促进糖尿病溃疡愈合的技术
溃疡边缘的细胞(角质形成细胞)。层粘连蛋白5(LAM 5)
细胞信号通路是本研究的重点。跨学科的
该团队将在糖尿病患者和小鼠身上进行拟议的实验。这
申请将检验三个一般假设:1.
糖尿病溃疡的闭合是角质形成细胞迁移失败,尽管有明显的
溃疡边缘角质形成细胞增殖。2.LAM-5介导的信号转导
是角质形成细胞迁移所必需的,在糖尿病中受损。3.
LAM 5细胞信号通路的阐明将导致新的方法
刺激角质形成细胞迁移,加速糖尿病溃疡愈合。按顺序
为了验证这些假设,我们将实现以下具体目标:
具体目标1.确定糖尿病患者的慢性溃疡的特征
糖尿病和正常人/小鼠对LAM-5的急性创伤
异构体和LAM 5mRNA,LAM 5相关整合素α6-β4
α3-β1和增殖标记Ki67。具体目标2.评估
LAM 5亚域的功能以及设计和生产重组
LAM亚型5.特异性靶点3.评价角质形成细胞
调节LAM-5的合成和沉积,并评价LAM-5在
正常细胞和糖尿病细胞的迁移。具体目标4.评估效果
重组LAM-5亚型在db/db糖尿病创面的应用
并开发出可最大限度提高治愈率的生物材料。
英文摘要
DESCRIPTION (adapted from the application)
One of the stated goals of Healthy People 2000 is to reduce the incidence of
lower extremity amputation in diabetic patients from the 1988 baseline rate of
8.2/1000 to a target incidence of 4.9/1000 in the year 2000. Despite efforts
directed at prevention, the rate of amputation has continued to rise in
patients with DM. A better understanding of the pathogenesis of diabetic ulcers
and novel treatment strategies are required to reverse the rising trend in the
rate of amputation. The goal of this application is to use new molecular
technologies to enhance healing of diabetic ulcers by increasing the migration
of cells (keratinocytes) at the ulcer margin. The laminin 5 (Lam 5)
cell-signaling pathway is the focus of this investigation. An interdisciplinary
team will conduct the proposed experiments in patients and mice with DM. This
application will test three general HYPOTHESES: 1. The principle deficit in
closure of diabetic ulcers is failure of keratinocyte migration despite marked
keratinocyte proliferation at the ulcer margin. 2. Lam 5 mediated signaling,
essential for keratinocyte migration, is impaired in diabetes mellitus. 3.
Clarification of Lam 5 cellsignaling pathways will lead to novel approaches to
stimulate keratinocyte migration and speed healing of diabetic ulcers. In order
to test these hypotheses we will carry out the following Specific Aims:
Specific Aim 1. Characterize chronic ulcers from patients with diabetes and
acute wounds from diabetic and normal human subjects/mice regarding Lam 5
isoforms and Lam 5 mRNA, the Lam 5 associated integrins alpha6-beta4
alpha3-beta1 and the proliferation marker Ki67. Specific Aim 2. Evaluate
functions for Lam 5 sub-domains as well as design and produce recombinant
isoforms of Lam 5. Specific Aim 3. Evaluate mechanisms by which keratinocytes
regulate synthesis and deposition of Lam 5, and evaluate the role of Lam 5 in
the migration of normal and diabetic cells. Specific Aim 4. Assess the effects
of application of recombinant Lam 5 isoforms to the wounds of db/db diabetic
mice and develop bioniaterials that elicit a maximal increase in healing rate.
期刊论文(7)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1002/jbm.a.32798
发表时间:
2010-09-15
期刊:
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
影响因子:
4.9
作者:
[Fukano, Y., Usui, M. L., Underwood, R. A., Isenhath, S., Marshall, A. J., Hauch, K. D., Ratner, B. D., Olerud, J. E., Fleckman, P.]
通讯作者:
Fleckman, P.
Ultrastructural localization of integrin subunits beta4 and alpha3 within the migrating epithelial tongue of in vivo human wounds.
整合素亚基β4和α3在体内人类伤口迁移上皮舌内的超微结构定位。
DOI:
10.1369/jhc.2008.952176
发表时间:
2009
期刊:
The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society
影响因子:
--
作者:
[Underwood,RobertA, Carter,WilliamG, Usui,MarciaL, Olerud,JohnE]
通讯作者:
Olerud,JohnE
Training for Investigative Dermatology
-
批准号:8105040
-
项目类别:
-
资助金额:$15.12万
-
财政年份:2009
-
负责人:JOHN Everett OLERUD
-
依托单位:
Training for Investigative Dermatology
-
批准号:7872870
-
项目类别:
-
资助金额:$17.35万
-
财政年份:2009
-
负责人:JOHN Everett OLERUD
-
依托单位:
Training for Investigative Dermatology
-
批准号:8291391
-
项目类别:
-
资助金额:$15.73万
-
财政年份:2009
-
负责人:JOHN Everett OLERUD
-
依托单位:
Training for Investigative Dermatology
-
批准号:7634778
-
项目类别:
-
资助金额:$18.27万
-
财政年份:2009
-
负责人:JOHN Everett OLERUD
-
依托单位:
Percutaneous Devices Permitting Skin Cell Attachment
-
批准号:7093475
-
项目类别:
-
资助金额:$48.76万
-
财政年份:2005
-
负责人:JOHN Everett OLERUD
-
依托单位:
Percutaneous Devices Permitting Skin Cell Attachment
-
批准号:7415026
-
项目类别:
-
资助金额:$49.23万
-
财政年份:2005
-
负责人:JOHN Everett OLERUD
-
依托单位:
Percutaneous Devices Permitting Skin Cell Attachment
-
批准号:6987044
-
项目类别:
-
资助金额:$49.77万
-
财政年份:2005
-
负责人:JOHN Everett OLERUD
-
依托单位:
Percutaneous Devices Permitting Skin Cell Attachment
-
批准号:7214683
-
项目类别:
-
资助金额:$48.77万
-
财政年份:2005
-
负责人:JOHN Everett OLERUD
-
依托单位:
Percutaneous Devices Permitting Skin Cell Attachment-Inhibiting Biofilm Formation
-
批准号:7192310
-
项目类别:
-
资助金额:$12.8万
-
财政年份:2004
-
负责人:JOHN Everett OLERUD
-
依托单位:
THE ROLE OF LAMININ 5 IN DIABETIC ULCER HEALING
-
批准号:6524410
-
项目类别:
-
资助金额:$47.31万
-
财政年份:2000
-
负责人:JOHN Everett OLERUD
-
依托单位:
THE ROLE OF LAMININ 5 IN DIABETIC ULCER HEALING
-
批准号:6311267
-
项目类别:
-
资助金额:$48.15万
-
财政年份:2000
-
负责人:JOHN Everett OLERUD
-
依托单位:
THE ROLE OF LAMININ 5 IN DIABETIC ULCER HEALING
-
批准号:6381995
-
项目类别:
-
资助金额:$46.15万
-
财政年份:2000
-
负责人:JOHN Everett OLERUD
-
依托单位:
THE ROLE OF LAMININ 5 IN DIABETIC ULCER HEALING
-
批准号:6647082
-
项目类别:
-
资助金额:$48.51万
-
财政年份:2000
-
负责人:JOHN Everett OLERUD
-
依托单位:
ULTRASONIC ASSESSMENT OF SURGICAL WOUNDS
-
批准号:3160044
-
项目类别:
-
资助金额:$27.96万
-
财政年份:1989
-
负责人:JOHN Everett OLERUD
-
依托单位:
ULTRASONIC ASSESSMENT OF SURGICAL WOUNDS
-
批准号:3160042
-
项目类别:
-
资助金额:$29.68万
-
财政年份:1989
-
负责人:JOHN Everett OLERUD
-
依托单位:
ULTRASONIC ASSESSMENT OF SURGICAL WOUNDS
-
批准号:3160043
-
项目类别:
-
资助金额:$27.66万
-
财政年份:1989
-
负责人:JOHN Everett OLERUD
-
依托单位:
DERMATOLOGY TRAINING
-
批准号:2077623
-
项目类别:
-
资助金额:$10.03万
-
财政年份:1975
-
负责人:JOHN Everett OLERUD
-
依托单位:
DERMATOLOGY TRAINING
-
批准号:6886794
-
项目类别:
-
资助金额:$18.78万
-
财政年份:1975
-
负责人:JOHN Everett OLERUD
-
依托单位:
DERMATOLOGY TRAINING
-
批准号:2077624
-
项目类别:
-
资助金额:$0.58万
-
财政年份:1975
-
负责人:JOHN Everett OLERUD
-
依托单位:
DERMATOLOGY
-
批准号:3531775
-
项目类别:
-
资助金额:$11.21万
-
财政年份:1975
-
负责人:JOHN Everett OLERUD
-
依托单位:
海外基金