Adiponectin inhibits activation and injury of lung endothelium

脂联素抑制肺内皮细胞的活化和损伤

• 批准号: 8852162
• 负责人: Ross S Summer
• 金额: $ 38.17万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8852162
• 关键词: Acute Lung Injury; Adenovirus Vector; Adipocytes; Adipose tissue; Advanced Practice Nurse; Agonist; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Apoptotic; Area; Attenuated; Binding; Biological; Biology; Blood Vessels; Body fat; Cells; Complex; Critical Illness; Data; Distal; E-Selectin; Endocrine Glands; Endothelial Cells; Endothelium; Epidemic; Etiology; Foundations; Future; Gene Deletion; Genetic; Grant; H-Cadherin; Homeostasis; Hormones; Human; Hyperoxia; In Situ Hybridization; In Vitro; Infiltration; Inflammatory; Inflammatory Response; Injury; Investigation; Knock-out; Laboratories; Lung; Lung Inflammation; Lung diseases; Mediating; Metabolism; Molecular; Molecular Weight; Mus; Obesity; Patients; Phenotype; Play; Prevention therapy; Process; Proteins; Pulmonary artery structure; Reagent; Recombinants; Research; Role; Serum; Signal Pathway; Site; Small Interfering RNA; Stream; Structure of parenchyma of lung; Surface; Testing; Up-Regulation; Vascular Diseases; adipokines; adiponectin; cell injury; clinical investigation; design; gain of function; in vivo; interest; knock-down; lung injury; mortality; novel; pressure; prevent; pulmonary artery endothelial cell; receptor; research study; response to injury; tool; vascular inflammation

DESCRIPTION (provided by applicant): This grant studies the molecular interaction between lung and adipose tissue mediated by the adipocyte-derived hormone adiponectin. Adiponectin has been shown to act in murine lung to tonically inhibit endothelial cell activation and to limit injury originating from endothelial cell damage (e.g. hyperoxia). This proposal will utilize a broad range of genetic tools (e.g. adiponectin and adiponectin receptor deficient mice) and reagents (e.g. recombinant adiponectin protein, adenoviral vectors) to perform the first comprehensive examination of adiponectin's role in lung vascular homeostasis. Studies in Aim 1 will identify the oligomeric fractions and key structural domains mediating adiponectin's effects on lung endothelium and will elucidate the down-stream signaling pathways of adiponectin on lung endothelium. Studies in Aim 2 are designed to test the hypothesis that adiponectin mitigates lung injury to hyperoxia by activating anti- inflammatory and cyto-protective processes on lung endothelium. Finally, studies in Aim 3 will utilize in vitro and in vivo tools to identify the important adiponectin receptor mediating adiponectin's effects in lung. Taken together, studies in this grant will identify the molecular mechanisms by which APN regulates lung vascular processes in the hope of identifying new avenues of research in lung vascular biology and laying the foundation for the rational design of future clinical investigations examining APN in human lung disease.

描述(申请人提供)：这项资助研究脂肪细胞衍生荷尔蒙脂联素介导的肺和脂肪组织之间的分子相互作用。脂联素已被证明在小鼠肺中作用于张力抑制内皮细胞激活和限制由内皮细胞损伤(如高氧)引起的损伤。这项建议将利用广泛的遗传工具(例如脂联素和脂联素受体缺陷小鼠)和试剂(例如重组脂联素蛋白、腺病毒载体)来首次全面检查脂联素在肺血管稳态中的作用。目标1的研究将确定脂联素对肺内皮细胞影响的低聚组分和关键结构域，并将阐明脂联素对肺内皮细胞的下游信号通路。AIM 2中的研究旨在验证脂联素通过激活肺内皮细胞上的抗炎和细胞保护过程来减轻高氧所致肺损伤的假设。最后，AIM 3的研究将利用体外和体内工具来确定重要的脂联素受体介导脂联素在肺中的作用。综上所述，这项拨款的研究将确定APN调节肺血管过程的分子机制，希望找到肺血管生物学研究的新途径，并为未来合理设计APN在人类肺部疾病中的临床研究奠定基础。

项目成果

Extracellular ATP mediates the late phase of neutrophil recruitment to the lung in murine models of acute lung injury.

在急性肺损伤的小鼠模型中，细胞外 ATP 介导中性粒细胞募集到肺部的后期。

• DOI: 10.1152/ajplung.00229.2013
• 发表时间: 2014
• 期刊: American journal of physiology. Lung cellular and molecular physiology
• 作者: Shah,Dilip;Romero,Freddy;Stafstrom,William;Duong,Michelle;Summer,Ross
• 通讯作者: Summer,Ross

Acute respiratory distress syndrome: epidemiology and management approaches.

• DOI: 10.2147/clep.s28800
• 发表时间: 2012-01-01
• 期刊: Clinical epidemiology
• 影响因子: 3.9
• 作者: Walkey, Allan J;Summer, Ross;Alkana, Philip
• 通讯作者: Alkana, Philip

Obesity and pulmonary arterial hypertension: Is adiponectin the molecular link between these conditions?

• DOI: 10.4103/2045-8932.93542
• 发表时间: 2011-10
• 期刊: Pulmonary circulation
• 影响因子: 2.6
• 作者: Summer R;Walsh K;Medoff BD
• 通讯作者: Medoff BD

Role of Angiotensin II type 1 receptor on renal NAD(P)H oxidase, oxidative stress and inflammation in nitric oxide inhibition induced-hypertension.

• DOI: 10.1016/j.lfs.2015.01.005
• 发表时间: 2015-03-01
• 期刊: Life sciences
• 影响因子: 6.1
• 作者: Rincón J;Correia D;Arcaya JL;Finol E;Fernández A;Pérez M;Yaguas K;Talavera E;Chávez M;Summer R;Romero F
• 通讯作者: Romero F

Cavin1; a regulator of lung function and macrophage phenotype.

• DOI: 10.1371/journal.pone.0062045
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Govender P;Romero F;Shah D;Paez J;Ding SY;Liu L;Gower A;Baez E;Aly SS;Pilch P;Summer R
• 通讯作者: Summer R