课题基金 / 基金详情

Transforming Growth Factor Beta-Activated Kinase 1 (Tak1) in Retinal Microglial Inflammation

Transforming Growth Factor Beta-Activated Kinase 1 (Tak1) in Retinal Microglial Inflammation
转化生长因子 β 激活激酶 1 (Tak1) 在视网膜小胶质细胞炎症中的作用
批准号:
10438002
负责人:
TERI L BELECKY-ADAMS
金额:
$45.6万
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
未结题
起止时间:
2022-05-01 至 2025-04-30

项目摘要

项目成果

TERI L BELECKY-ADAMS的其他基金

相关文献

中文摘要
翻译
糖尿病视网膜病变与慢性异常炎症有关,这种炎症被认为在 神经血管单位功能的早期中断。关于细胞内信号的信息是不完整的 参与炎症信号上调的通路。识别更多的途径成员将导致 更多的治疗靶点将用于神经退行性疾病的治疗。这项建议的目的是 检测转化生长因子β激活的激酶1在激活核因子κB、p38和jnk中的作用 视网膜小胶质细胞中的多种途径,导致炎症因子转录增加。假设 抑制TAK1将减少糖尿病视网膜病变早期的炎症反应,并减少 神经血管单位将在体外使用分离的小胶质细胞进行测试,并在体内使用组合 链脲佐菌素(STZ)诱导的糖尿病小鼠小胶质细胞TAK1的条件性缺失。实验将会 利用小分子抑制剂,添加已知的炎症因子,微量注射,定量 聚合酶链式反应,Western印迹分析,多重酶联免疫吸附试验,以及 视网膜周细胞、微血管构筑、小胶质细胞、视网膜星形胶质细胞、神经节细胞和Müler胶质细胞的定量 整册和版面。
英文摘要
Diabetic retinopathy is associated with chronic aberrant inflammation that is proposed to play a critical role in the early disruption of neurovascular unit function. There is incomplete information about intracellular signaling pathways involved in upregulation of inflammatory signals. Identification of more pathway members will lead to more therapeutic targets to be used in treatment of neurodegenerative diseases. This proposal is aimed at testing the role of transforming growth factor β-activated kinase 1 (TAK1) in activation NFκB, p38, and JNK pathways in retinal microglia, resulting in increased transcription of inflammatory factors. The hypothesis that inhibition of TAK1 will reduce inflammation in the early stages of diabetic retinopathy and reduce changes to the neurovascular unit will be tested in vitro using isolated microglial cells and in vivo using a combination of streptozotocin (STZ)-induced diabetes in mice with conditional loss of TAK1 in microglia. Experiments will utilize small molecule inhibitors, addition of known inflammatory factors, microinjections, quantitative polymerase chain reactions, Western blot analysis, multiplex enzyme-linked immunosorbent assays, and quantitation of pericytes, microvasculature, microglia, retinal astrocytes, ganglion cells, and Müller glia in retinal wholemounts and sections.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Mechanisms of Astrocyte Development
Astrocyte Development and Reactive Gliosis
Astrocyte Development and Reactive Gliosis
Astrocyte Development and Reactive Gliosis