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.

视网膜周细胞是邻近内皮细胞的收缩细胞，并为其提供支持毛细血管，对于眼睛早期视网膜脉管系统的调节至关重要。糖尿病视网膜病变的特点是视网膜周细胞的丧失，这导致包括血管生成在内的晚期病理学的发展。关于糖尿病视网膜病变的病因学，即引起视网膜周细胞丢失的细胞凋亡途径我们的初步研究表明单核细胞来源的巨噬细胞会分泌。 TGFβ1，诱导 TGFβ1 诱导的促凋亡 BIGH3 的表达和分泌蛋白（TGFβ——诱导基因人类克隆 3）导致内皮细胞凋亡视网膜周细胞的这种级联事件被归因于视网膜的主要原因。周细胞凋亡和糖尿病视网膜病变是糖尿病前期。糖尿病视网膜病变的生物标志物和干预的潜在治疗靶点在本研究中，我们捕获了类似的巨噬细胞-TGFβ-BIGH3。途径可能诱导视网膜周细胞凋亡。我们将研究之间的相互作用。内皮细胞和视网膜周细胞，以及巨噬细胞对视网膜周细胞表达的作用此外，我们还将研究 BIGH3 对 TGFβ 的反应以及视网膜周细胞凋亡。 BIGH3与跨膜信号蛋白受体整合素的关联及其作用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细胞凋亡。影响糖尿病视网膜病变的分子途径，它将提供治疗机会学生学员将参与这些研究。项目，提供生物医学研究的宝贵经验。