Cell-Meditated Inflammatory Pathway and Diabetic Retinopathy

细胞介导的炎症途径和糖尿病视网膜病变

基本信息

批准号：
10368669
负责人：
ANDREW T C TSIN
金额：
$ 35.51万
依托单位：
UNIVERSITY OF TEXAS RIO GRANDE VALLEY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-01 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10368669
关键词：
APAF1 gene Advanced Development Affect Antibodies Apoptosis Apoptotic Biological Assay Biological Markers Biomedical Research CASP3 gene CASP8 gene CASP9 gene Capillary Endothelial Cell Caspase Cell Adhesion Cell Communication Cell Surface Receptors Cells Cellular biology Cessation of life Coculture Techniques Development Diabetes Mellitus Diabetic Retinopathy Disease Early Intervention Early treatment Endothelial Cells Ensure Enzymes Etiology Event Eye Eye diseases Funding Gene Expression Genes Goals Grant Hispanic Human Human Cloning Individual Inflammatory Integrin alpha3 Integrins Intervention Joints Knowledge Laboratories Lead Learning Literature Measures Mediating Minority Groups Modeling Molecular Molecular Biology Oligonucleotides Pathology Pathway interactions Peptide Hydrolases Peptides Pericytes Prediabetes syndrome Proteins Regulation Reporting Research Research Project Grants Retina Role Signal Transduction Signaling Protein Small Interfering RNA Students System TGFBI gene Therapeutic Intervention Time Transforming Growth Factor beta angiogenesis base cytochrome c diabetic experience inhibitor innovation macrophage monocyte novel osteosarcoma pandemic disease protein aminoacid sequence receptor response synthetic peptide therapeutic target

项目摘要

Retinal pericytes are contractile cells adjacent to and provide support for endothelial cells of capillaries, which are essential in the regulation of retinal vasculature in the eye. Early stages of diabetic retinopathy are characterized by the loss of retinal pericytes, which lead to the development of advanced-stage pathology including angiogenesis. Although much is known about the etiology of diabetic retinopathy, the apoptotic pathway that incites retinal pericyte loss remains unclear. Our preliminary studies reveal that monocyte-derived macrophages secrete TGFβ1, which induces the expression and secretion of a TGFβ1-Induced, pro-apoptotic BIGH3 protein (TGFβ –Induced Gene Human Clone 3) leading to apoptosis of endothelial cells and retinal pericytes. This cascade of events has been attributed to the primary cause of retinal pericyte apoptosis and diabetic retinopathy. Macrophage TGF-β1 and BIGH3 are prediabetic biomarkers, and potential therapeutic targets for intervention of diabetic retinopathy for diabetic individuals. In the present study, we hypothesize that a similar macrophage-TGFβ–BIGH3 pathway may induce apoptosis in retinal pericytes. We will investigate the interaction between endothelial cells and retinal pericytes, as well as macrophages’ role on retinal pericyte expression of BIGH3 in response to TGFβ, and retinal pericyte apoptosis. Furthermore, we will also study the association of BIGH3 with integrin, a trans-membrane signaling protein receptor and its role to mediate retinal pericyte apoptosis. This novel study focuses on macrophage-mediated molecular pathway to impact diabetic retinopathy and it will provide opportunities of therapeutic intervention of this ocular eye disorder. Student trainees will be involved in these research projects, providing valuable experience on biomedical research.

视网膜周细胞是收缩细胞，与之相邻，并为毛细血管，这对于对视网膜脉管系统的调节至关重要。早期阶段糖尿病性视网膜病的特征是视网膜周周的丧失，这导致开发包括血管生成在内的晚期病理。虽然众所周知关于糖尿病性视网膜病的病因，促进视网膜周细胞损失的凋亡途径仍然不清楚。我们的初步研究表明，单核细胞衍生的巨噬细胞分泌 TGFβ1，诱导TGFβ1诱导的促凋亡Bigh3的表达和分泌蛋白质（TGFβ - 诱导的基因人克隆3）导致内皮细胞凋亡和视网膜周细胞。这串联的事件归因于视网膜的主要原因周细胞凋亡和糖尿病性视网膜病。巨噬细胞TGF-β1和Bigh3是糖尿病前期生物标志物和潜在的治疗靶标，用于干预糖尿病性糖尿病患者在本研究中，我们假设类似的巨噬细胞-TGFβ– Bigh3 途径可能诱导永久性周细胞的凋亡。我们将研究内皮细胞和永久性周细胞，以及巨噬细胞在永久性周细胞表达中的作用 Bigh3响应TGFβ和视网膜周细胞凋亡。此外，我们还将学习 Bigh3与整合素，反膜信号蛋白受体及其作用的关联介导视网膜周细胞凋亡。这项新研究的重点是巨噬细胞介导的撞击糖尿病性视网膜病的分子途径，它将提供治疗的机会这种眼部眼部障碍的干预。学生学员将参与这些研究项目，为生物医学研究提供宝贵的经验。