G 蛋白信号传导调节因子 4 在急性肾损伤中的作用-猫眼课题宝

G 蛋白信号传导调节因子 4 在急性肾损伤中的作用

批准号：

9028611

负责人：

Andrew Michael Siedlecki

金额：

$0.07万

依托单位：

BRIGHAM AND WOMEN'S HOSPITAL

依托单位国家：

美国

项目类别：

财政年份：

2011

资助国家：

美国

项目状态：

已结题

起止时间：

2011-07-15 至 2016-04-30

来源：

https://reporter.nih.gov/project-details/9028611

关键词：

Acute Acute Renal Failure with Renal Papillary Necrosis Advisory Committees Affect Angiotensin II Applications Grants Area Avidity Blood Vessels Bone Marrow Cell Culture Techniques Cells Complement Cyclosporine Development Diabetes Mellitus Digestive System Disorders Disease Endothelin A Receptor Endothelin-1 Environment Exhibits Fellowship G-Protein-Coupled Receptors GTP-Binding Protein Regulators GTP-Binding Proteins GTPase-Activating Proteins Goals Heterotrimeric GTP-Binding Proteins Hospitals Individual Inflammatory Inflammatory Response Injury Institutes Institution Investigation Ischemia Kidney Kidney Diseases Kidney Transplantation Knock-out Knockout Mice Laboratories Ligands Macrophage Activation Mediating Mentored Clinical Scientist Development Award (K08)Mentorship Mononuclear Mus Nephrology Phagocytes Phase Physicians Physiological Play Principal Investigator Process Program Development Proteins Publishing RGS Proteins Receptor Activation Renal Blood Flow Renal function Reperfusion Injury Reperfusion Therapy Reporting Research Research Project Grants Resources Role Scientist Signal Transduction Smooth Muscle Myocytes Therapeutic Time Training United States Vascular Diseases Vascular Endothelial Cell Vascular System Vascular blood supply Warm Ischemia Wild Type Mouse Work arteriole bosentan career career development density experience in vivo injured kidney vascular structure macrophage monocyte monocyte chemoattractant protein 1 receptor mouse model normotensive overexpression prevent protein activation renal ischemia research study response skills tool vasoconstriction

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英文摘要

DESCRIPTION (provided by applicant): This revised grant proposal outlines a five year program for the development of an academic research career in nephrology. The principal investigator (PI) has experience in laboratory investigation and completed nephrology fellowship training. He is currently developing his skills in the investigation of acute kidney injury and the component parts of ischemia and reperfusion . He will receive his primary mentorship from Dr. Keith Hruska, an internationally recognized expert in the field of vascular disease and kidney injury with extensive experience in the training of physician-scientists. Dr. Hruska's expertise will be augmented by a scientific advisory committee comprised of individuals who will provide assistance in defined areas germane to the investigation. The academic environment of the PI's institution has developed substantial resources for the career development of young scientists complemented by a host of core research centers. The research component of this proposal will focus on the RGS4 protein, with known function in the vasculature and inflammatory cells. The renal-specific activity of Regulator of G protein Signaling 4 (RGS4) will be investigated as it applies to ischemia and subsequent reperfusion injury. Ischemia/reperfusion kidney injury is the most common form of acute kidney disease and yet there are few therapeutic options. RGS proteins have the potential to influence the disease process of acute kidney injury, but this area of study is largely unexplored. We hypothesize that RGS4 regulates vasoconstriction during renal ischemia and mitigates the inflammatory response of early renal reperfusion injury. RGS4 has recognized activity in the vascular system. Our findings show RGS4 depletion decreases renal blood flow after acute ischemic injury and is compounded by an early influx of macrophages. Research tools will include genetically modified mouse models that, overexpress RGS4, do not express RGS4 in vascular smooth muscle cells alone, or do not express RGS4 globally.

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