Histopathology Core

组织病理学核心

• 批准号: 10155089
• 负责人: VIVETTE D'AGATI
• 金额: $ 16.69万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-15 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10155089
• 关键词: AIDS-Associated Nephropathy; Acetylation; African American; Agonist; Animal Model; Archives; Bioinformatics; Biopsy; Biopsy Specimen; Bromodomain; Chronic; Chronic Kidney Failure; Clinical; Consequences of HIV; Data Storage and Retrieval; Databases; Development; Diabetes Mellitus; Diabetic Nephropathy; Diagnosis; Disease; Electron Microscopy; End stage renal failure; Endothelium; Epidemic; Epithelial Cells; Genetic Transcription; HIV; HIV Infections; HIV Seropositivity; Health; Histologic; Histopathology; Human; Immunofluorescence Immunologic; Immunofluorescence Microscopy; Immunohistochemistry; Incidence; Individual; Infection; Inflammatory; Inflammatory Response; Injury; Investigation; Kidney; Kidney Diseases; Light; Mediating; Microscopic; Mitochondria; Mus; NF-kappa B; Pathogenicity; Pathologic; Pathology; Pathway interactions; Patients; Program Research Project Grants; Research; Research Support; Risk; Role; SIRT1 gene; STAT3 gene; Sampling; Source; Standardization; T-Lymphocyte; Techniques; Tissues; Transgenic Mice; Tubular formation; Tumor-infiltrating immune cells; Virus; Work; antiretroviral therapy; base; comorbidity; data exchange; experimental study; gut microbiome; in vitro Model; inhibitor/antagonist; kidney biopsy; light microscopy; mouse model; programs; renal epithelium; repository; sample archive; senescence; trend

Abstract: Renal disease in HIV-infected patients has evolved over the 3 decades since the outset of the infection. Whereas HIV-associated nephropathy (HIVAN) manifesting collapsing glomerulopathy, tubular microcysts and endothelial tubuloreticular inclusions predominated early in the epidemic, the incidence of HIVAN has declined following the introduction of anti- retroviral therapy. Despite this trend, the incidence of ESRD has remained unchanged, reflecting the development of other histopathology. This proposal will explore the long-term consequences of HIV infection in the kidney beyond HIVAN. The role of Core B will be to provide technical and interpretative support in light microscopy, immunohistochemistry, immunofluorescence and electron microscopy in mouse and human kidney tissues for all projects. For Specific Aim 1, archived kidney biopsy tissue from HIV positive patients will be selected based on histopathologic diagnosis for investigation of inflammatory pathways identified in the in vitro models using immunohistochemistry and immunofluorescence. In Specific Aim 2, renal pathology in Tg26 mice with different intestinal microbiome will be evaluated and immunostaining performed to quantify immune cell infiltrates. For Specific Aim 3, the hypothesis that chronic HIV infection promotes comorbid disease though enhanced pro- inflammatory response via SIRT-1-regulated NF-kB and STAT3 acetylation and mitochondrial injury will be investigated in murine kidneys and validated in human kidney tissues. Core B will collaborate with the Clinical Core to identify appropriate kidney biopsy samples from the Core C repository or from anonymized archived samples in the Columbia biopsy database as needed.

抽象的： 自从艾滋病毒感染患者的肾脏疾病以来，在30年中已经发展了 感染。而与HIV相关的肾病（Hivan）表现出崩溃 肾小球病，管状微型细胞和内皮肾小管夹杂物占主导地位 在流行病的早期，希文的发生率下降了 逆转录病毒疗法。尽管这种趋势，ESRD的发病率保持不变， 反映其他组织病理学的发展。该建议将探讨长期的 Hivan以外的肾脏感染的后果。核心B的作用将是 在光学显微镜，免疫组织化学中提供技术和解释性支持， 所有所有人的免疫荧光和电子显微镜 项目。对于特定的目标1，来自HIV阳性患者的存档肾脏活检组织将是 根据组织病理学诊断选择以研究炎症途径 使用免疫组织化学和免疫荧光在体外模型中鉴定。在 特定的目标2，具有不同肠道微生物组的TG26小鼠中的肾脏病理学将是 评估和免疫染色以量化免疫细胞浸润。对于特定的目标3， 慢性艾滋病毒感染促进了合并症的假说，尽管增强了疾病 SIRT-1调节的NF-KB和STAT3乙酰化和线粒体的炎症反应 将在鼠肾脏中研究损伤，并在人类肾脏组织中进行验证。核心核心 与临床核心合作，从核心C中识别适当的肾脏活检样本 根据需要，在哥伦比亚活检数据库中的存储库或匿名的存档样本。