Cell-Mediated Inflammatory Pathway and Diabetic Retinopathy-Administrative Supplement

细胞介导的炎症途径和糖尿病视网膜病变-管理补充剂

• 批准号: 10789444
• 负责人: ANDREW T C TSIN
• 金额: $ 14.28万
• 依托单位: UNIVERSITY OF TEXAS RIO GRANDE VALLEY
• 依托单位国家: 美国
• 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/10789444
• 关键词: Administrative Supplement; Advanced Development; Apoptosis; Apoptotic; Biological Markers; Biomedical Research; Capillary Endothelial Cell; Cells; Data; Diabetes Mellitus; Diabetic Retinopathy; Disease; Doctor of Philosophy; Endothelial Cells; Ensure; Etiology; Event; Eye; Eye diseases; Genes; Grant; Hispanic; Human Cloning; Individual; Induction of Apoptosis; Inflammatory; Institutionalization; Integrins; Intervention; Knowledge; Learning; Macrophage; Mediating; Membrane; Mentors; Mentorship; Minority Groups; Molecular; Outcome; Parents; Pathology; Pathway interactions; Pericytes; Prediabetes syndrome; Program Evaluation; Proteins; Regulation; Reproducibility; Research; Research Project Grants; Retina; Role; Signaling Protein; Students; TGFBI gene; Talents; Therapeutic Intervention; Training; Training Programs; Transforming Growth Factor beta; United States National Institutes of Health; angiogenesis; diabetic; education research; equity, diversity, and inclusion; experience; experimental study; faculty mentor; graduate student; innovation; interest; monocyte; novel; pandemic disease; peer coaching; programs; receptor; response; success; therapeutic target; timeline; undergraduate student

Abstract: 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.

摘要： 视网膜周细胞是与视网膜血管内皮细胞相邻的可收缩细胞， 毛细血管，其在眼睛中的视网膜血管系统的调节中是必需的。初期 糖尿病性视网膜病变的特征在于视网膜周细胞的损失，这导致了 包括血管生成在内的晚期病理学的发展。虽然我们知道 关于糖尿病视网膜病变的病因，引发视网膜周细胞损失的凋亡途径， 仍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，其诱导TGFβ1诱导的促凋亡BIGH 3的表达和分泌 蛋白质（TGFβ诱导基因人克隆3）导致内皮细胞凋亡， 视网膜周细胞这一系列事件被归因于视网膜病变的主要原因。 周细胞凋亡与糖尿病视网膜病变的关系巨噬细胞TGF-β1和BIGH 3是糖尿病前期 糖尿病视网膜病变的生物标志物和潜在的治疗靶点 个体在本研究中，我们假设一个类似的巨噬细胞-TGF β-BIGH 3 途径可能诱导视网膜周细胞凋亡。我们将研究 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 BIGH 3对TGFβ的反应以及视网膜周细胞凋亡。此外，我们还将研究 BIGH 3与跨膜信号蛋白受体整合素结合及其作用 介导视网膜周细胞凋亡。这项新的研究重点是巨噬细胞介导的 分子途径影响糖尿病视网膜病变，它将提供机会， 这种眼部疾病的干预。实习生将参与这些研究 项目，为生物医学研究提供宝贵经验。