权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Roles of Growth Factors on Corneal Morphogenesis

生长因子对角膜形态发生的作用

基本信息

批准号：
8383107
负责人：
WINSTON W KAO
金额：
$ 43.65万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-07-01 至 2014-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8383107
关键词：
Abbreviations Ablation Accounting Activating Transcription Factor 2 Adenovirus Vector Adult Alleles Animal Experimentation Animals Antibodies Basement membrane Binding Bromodeoxyuridine Caliber Cell Death Cell Proliferation Cell physiology Collaborations Complex Cornea Corneal Diseases Corneal Injury DNA Double Strand Break Data Debridement Dimerization Dominant-Negative Mutation Doxycycline Epithelial Cell Proliferation Epithelium Eye Family Fluorescein Gene Deletion Genes Genetic Growth Factor Healed Homeostasis Hour Immunohistochemistry Immunoprecipitation In Vitro Injury Integrins Intracellular translocation Luciferases MAP Kinase Gene MAPK8 gene Measures Mediating Molecular Molecular Biology Morphogenesis Mus Pathway interactions Pattern Phase Phosphorylation Play Protein Biosynthesis Proteins Receptor Signaling Reporter Reverse Transcriptase Polymerase Chain Reaction Role SP600125 Signal Pathway Signal Transduction Staining method Stains Stress Tetanus Helper Peptide Transcription Factor AP-1 Transforming Growth Factors Transgenes Tumor Suppressor Proteins Variant Virus Vision Western Blotting Wild Type Mouse Wound Healing base cell motility corneal epithelium design effective therapy feeding healing in vivo inhibitor/antagonist injured member migration mouse model mutant neutralizing antibody overexpression receptor repaired research study restoration small hairpin RNA therapy design time interval transcription factor

项目摘要

Kao, Winston W.-Y. Transforming growth factor ¿ (TGF-¿) has a pivotal role in corneal wound healing. Previous studies revealed that activation of p38MAPK and Smad signaling pathway have distinct roles in mediating TGF-¿ signaling of corneal epithelium debridement and keratectomy, respectively. Such differences can be explained by the fact that healing epithelium of debridement migrates on basement membrane, whereas that of keratectomy migrates on collagenous matrix of denuded stroma, resulting in distinct integrin expression patterns in migrating epithelium within 1 hour of injuries. Thus, we hypothesize that interaction of different integrins with TGF-¿ receptors accounts for the difference in TGF-¿ signaling pathways, i.e., activation of p38MAPK in epithelium debridement and Smads cascades in keratectomy (Hypothesis 1). It has also been found that suppression of cell proliferation and activation of Activating Transcription Factor 2 (ATF2) are independent of TGF-¿ signaling following epithelium debridement. Thus, the activation of ATF2 by an alternative pathway, i.e., JNK, and its subsequent formation of Activating Protein-1 transcription factor (AP-1) complex plays a key role in the suppression of epithelial cell proliferation in the early healing phase of corneal injury (Hypotheisis 2). Specific Aim 1 will identify and characterize roles of integrins in TGF-¿ signaling pathways during the healing of corneal epithelium debridement and keratectomy using tritransgenic Cre-LoxP mouse models, i.e., Krt12rtTA/rtTA/tet-O-Cre/Tbr2f/f and Krt12rtTA/rtTA/tet-O-Cre/Smad4f/f in which floxed Tbr2 and Smad4 genes are ablated specifically in corneal epithelium upon doxycycline induction so that one can determine potential variations in signaling pathways in the absence and presence of Tbr2 and Smad4 (Aim 1A), to examine roles of integrins in mediating TGF-¿ receptor signaling (Aim 1B) and to examine efficacy of p38MAPK¿ and Smad7 on modulation of cell migration and proliferation during wound healing (Aim 1C). Specific Aim 2 will elucidate roles of ATF2 and AP-1 in suppression of cell proliferation during corneal wound healing by identification of ATF2 and/or AP-1 complexes in healing epithelium of corneal epithelium debridement and keratectomy using immunoprecipitation and western blot analysis (Aim 2A), determine involvement of ATF2 in suppression of cell proliferation during healing of epithelium debridement by overexpression of dominant negative ATF2 and ¿N-ATF2 mutant proteins (Aim 2B), and to determine effects of JNK and p38MAPK inhibitors on activation of ATF2 during corneal wound healing (Aim2C). These experiments will yield useful information for restoration of normal vision by intervening TBR2 and ATF2 signaling pathways of injured corneas.

温斯顿·高，w - y。

项目成果

期刊论文数量（21）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Sonic hedgehog expression and role in healing corneal epithelium

DOI：
10.1167/iovs.04-0001
发表时间：
2004-08-01
期刊：
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
影响因子：
4.4
作者：
Saika, S;Muragaki, Y;Kao, WWY
通讯作者：
Kao, WWY

Clinical and histopathological features and immunoreactivity of human choroidal and ciliary melanomas as prognostic factors for metastasis and death.

人类脉络膜和睫状体黑色素瘤的临床和组织病理学特征以及免疫反应性作为转移和死亡的预后因素。

DOI：
10.1007/s00417-011-1769-7
发表时间：
2011
期刊：
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie
影响因子：
0
作者：
Simões,CamilaC;Call,MindyK;Corrêa,ZéliaM;Spaulding,AbbotG;Augsburger,JamesJ
通讯作者：
Augsburger,JamesJ

Repressed Wnt Signaling Accelerates the Aging Process in Mouse Eyes.

抑制 Wnt 信号会加速小鼠眼睛的衰老过程。

DOI：
10.1155/2019/7604396
发表时间：
2019
期刊：
Journal of ophthalmology
影响因子：
1.9
作者：
Zhang,Yujin;Jeffrey,Joseph;Dong,Fei;Zhang,Jianhua;Kao,WinstonW-Y;Liu,Chia-Yang;Yuan,Yong
通讯作者：
Yuan,Yong

Therapeutic effects of adenoviral gene transfer of bone morphogenic protein-7 on a corneal alkali injury model in mice

腺病毒基因转染骨形态发生蛋白7对小鼠角膜碱损伤模型的治疗作用