Stanniocalcin-1, a novel anti-inflammatory protein

Stanniocalcin-1，一种新型抗炎蛋白

基本信息

批准号：
8515390
负责人：
DAVID SHEIKH-HAMAD
金额：
$ 31.58万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-08-01 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8515390
关键词：
A Mouse Adherence Adherens Junction Adipocytes Adverse effects Anti-Glomerular Basement Membrane Disease Anti-Inflammatory Agents Anti-inflammatory Apical Apoptosis Attenuated Biotin Blood Vessels Bone Marrow Calcium Cell Adhesion Molecules Cell Proliferation Chemotactic Factors Confocal Microscopy Cycloheximide Cytomegalovirus Dactinomycin Data Dextrans Diphtheria Toxin Disease Endothelial Cells Endothelium Evans blue stain Exhibits Flow Cytometry Gene Delivery Generations Glomerulonephritis Half-Life Histology Homologous Gene ITGAM gene Immunofluorescence Microscopy Infiltration Inflammation Inflammation Mediators Inflammatory Injection of therapeutic agent Injury Kidney Label Lead Mediating Messenger RNA Methods Microbubbles Mitochondria Molecular Weight Mus Pathogenesis Pathway interactions Permeability Pharmaceutical Preparations Phase Plasmids Play Post-Transcriptional Regulation Production Proteins Reactive Oxygen Species Recombinants Recovery Regulation Renal function Reporter Resolution Role Serum Small Interfering RNA Staging Superoxides Surface T-Lymphocyte TNF gene Texas red Thermogenesis Tight Junctions Transgenic Mice Translations UCP2 protein Ultrasonography Up-Regulation Vascular Permeabilities Western Blotting attenuation cadherin 5 chemokine claudin-1 protein conventional therapy cytokine dextran glomerular basement membrane human STC1 protein in vivo macrophage migration monolayer novel occludin overexpression protective effect protein expression protein kinase C zeta research study response small hairpin RNA transgene expression

项目摘要

Macrophages are important mediators of inflammation. Our data show stanniocalcin-1 (STC1) decreases macrophage response to chemoattractants and migration across an endothelial monolayer. STC1 also diminishes superoxide generation in macrophages, by inducing uncoupling protein-2 (UCP2), and inhibits the NF-¿B pathway. In cultured endothelial cells, STC1 inhibits cytokine-induced changes in permeability and tight junction protein expression. STC1 transgenic mice, which exhibit elevated serum levels and preferential expression of STC1 in macrophages and endothelium, display less inflammatory macrophages in the glomeruli during anti-glomerular basement membrane (GBM) disease, resulting in kidney protection. Overall hypothesis: STC1 suppresses inflammation through inhibition of macrophage recruitment and function, and cytokine-induced increase in endothelial permeability. In Specific Aim I, we will determine mechanisms of UCP2 upregulation by STC1 and the role of superoxide in STC1-mediated inhibition of NF-¿B in macrophages. In Specific Aim II, we will determine the effect of STC1 on cytokine-induced changes in expression and assembly of tight junction proteins in cultured primary kidney endothelial cells. In Specific Aim III, in the context of anti-GBM disease, we will examine endothelial permeability of native kidney vessels, as well as kidney inflammation and function, after kidney endothelium-specific or macrophage-specific overexpression or deletion of STC1.

巨噬细胞是炎症的重要介体。我们的数据显示Stanniocalcin-1（STC1）下降巨噬细胞对趋化剂的反应和跨内皮单层迁移。 STC1也是如此通过诱导解偶联蛋白2（UCP2）来减少巨噬细胞中的超氧化物的产生，并抑制 nf-€b途径。在培养的内皮细胞中，STC1抑制细胞因子诱导的渗透性变化和紧密的变化结蛋白表达。 STC1转基因小鼠，暴露了升高的血清水平和优先 STC1在巨噬细胞和内皮中的表达，在Glomerulli中表现出较少的炎症性巨噬细胞在抗斜体基底膜（GBM）疾病期间，导致肾脏保护。全面的假设：STC1通过抑制巨噬细胞募集和功能来抑制注射，以及细胞因子诱导的内皮渗透性增加。在特定目的I中，我们将确定 UCP2在STC1上的上调以及超氧化物在STC1介导的巨噬细胞中NF- - B的抑制作用中的作用。在特定的目标II中，我们将确定STC1对细胞因子诱导的表达变化和培养的原代肾脏内皮细胞中紧密连接蛋白的组装。在特定的目标III中抗GBM疾病的背景，我们将检查本地肾脏视频的内皮渗透性以及肾脏内皮特异性或巨噬细胞特异性过表达之后，肾脏炎症和功能或删除STC1。