Genetic and Molecular Mechanisms of Renal Injury

肾损伤的遗传和分子机制

• 批准号: 7258910
• 负责人: HANNA E ABBOUD
• 金额: $ 96.34万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7258910
• 关键词: 1-Phosphatidylinositol 3-Kinase; 15q; Address; Adult; Affect; Age; Albumins; Albuminuria; American; Angiotensin II; Angiotensins; Animal Model; Animals; Apoptosis; Applications Grants; Applied Research; Arachidonic Acids; Area; Arts; Attenuated; BRCA1 gene; Basic Science; Binding; Binding Proteins; Biochemical; Biochemical Genetics; Biochemistry; Biological Models; Biomedical Research; Biotechnology; Blood Platelets; Blood Vessels; Blood flow; Bos taurus; Bradykinin; Calcineurin; Candidate Disease Gene; Capillary Permeability; Cardiovascular Diseases; Cattle; Cell Cycle; Cell Cycle Proteins; Cell Differentiation process; Cell Proliferation; Cell physiology; Cells; Cellular biology; Cholinergic Agents; Chromosome Mapping; Chromosome Segregation; Chromosomes; Chromosomes, Human, Pair 15; Chronic; Clinical; Clinical Research; Collaborations; Colon Carcinoma; Communities; Complement; Consult; Core Facility; Country; Creatinine; Cross-Sectional Studies; Cutaneous; DNA Sequence; DNA biosynthesis; DNA chemical synthesis; Data; Death Rate; Detection; Development; Diabetes Mellitus; Diabetic Nephropathy; Diagnosis; Direct Costs; Discipline; Disease; Distal; Dorsal; E 10; Effectiveness; End stage renal failure; Endothelial Cells; Endothelin B Receptor; Enrollment; Environment; Enzyme Gene; Epidemiologist; Epithelial Cells; Equilibrium; Eukaryotic Initiation Factor-4E; Event; Exercise; Extracellular Matrix; Faculty; Family; Fellowship; Fingers; Forearm; Fostering; Foundations; Funding; Future; Gene Mutation; General Anesthesia; General Population; Genes; Genetic; Genetic Determinism; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Variation; Genotype; Glomerular Capillary; Glomerulonephritis; Goals; Grant; Growth Factor; Growth Factor Receptors; Hand; Health Sciences; Heat Stress Disorders; Heat-Shock Response; Hereditary Disease; Histology; Hormonal; Human; Human Genetics; Hybrids; Hyperemia; Hyperglycemia; Hyperinsulinism; Hypertension; Hypertrophy; IGF1 gene; Immigration; Individual; Infusion procedures; Injury; Institutes; Institution; Instruction; Insulin; Insulin Receptor; Insulin-Like Growth Factor I; International; Investigation; Ion Channel; Iontophoresis; Joints; Journals; Kidney; Kidney Diseases; Laboratories; Laminin; Lead; Leucine; Link; Linkage Disequilibrium; Location; Longitudinal Studies; Malignant Neoplasms; Manuscripts; Maps; Measurement; Mediating; Medicine; Membrane Proteins; Mesenchymal; Metabolic; Mexican Americans; Microalbuminuria; Mitochondria; Mitosis; Modeling; Molecular; Molecular Chaperones; Molecular Genetics; Morbidity - disease rate; Morphology; Motivation; Mus; Mutation; N(delta)-acetylornithine, -isomer; N-dodecanoylglutamic acid, -isomer, sodium salt; Names; Nature; Nephrology; Nerve; Non-Insulin-Dependent Diabetes Mellitus; Nuclear Protein; Nuclear Proteins; Numbers; Oxidation-Reduction; Papio; Participant; Pathogenesis; Pathology; Pathway interactions; Patients; Peer Review; Peptidyl-Dipeptidase A; Peripheral; Personal Satisfaction; Phenotype; Philadelphia; Phosphatidylinositols; Phosphorylation; Phosphotransferases; Physicians; Physiology; Platelet Factor 4; Platelet-Derived Growth Factor; Platelet-Derived Growth Factor Receptor; Play; Polycystic Kidney Diseases; Predisposition; Preparation; Prevalence; Prevention; Primates; Principal Investigator; Process; Prostate; Protein-Serine-Threonine Kinases; Proteins; Proteinuria; Proto-Oncogene Proteins c-akt; Protocols documentation; Proximal Kidney Tubules; Publications; Publishing; Purpose; Quantitative Trait Loci; Race; Rate; Rattus; Recording of previous events; Recruitment Activity; Reflex control; Regulation; Renin; Renin-Angiotensin System; Research; Research Activity; Research Personnel; Research Project Grants; Research Subjects; Research Training; Resources; Rest; Retinoblastoma; Retinoblastoma Protein; Rice; Risk; Role; Science; Scientist; Secondary to; Serine; Services; Severities; Sex Characteristics; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Single Nucleotide Polymorphism; Skin; Skin Temperature; Snake Venoms; Societies; Sports Medicine; Staging; Stimulation of Cell Proliferation; Stimulus; Structural Protein; Study Subject; Supervision; System; Temperature; Testing; Texas; Textbooks; Thinking; Thrombin; Tight Junctions; Time; Training; Transforming Growth Factor beta; Transgenes; Transgenic Animals; Transgenic Organisms; Translations; Trimeresurus; Tubular formation; United States; United States Department of Veterans Affairs; United States National Institutes of Health; Universities; Urine; Ursidae Family; VDAC1 gene; Variant; Vascular Endothelial Growth Factor Receptor; Vasodilation; Vasodilator Agents; Visit; Work; Yeasts; adipocyte differentiation; alpha-difluoromethyl-DOPA, -isomer; alpha-methylornithine dihydrochloride, -isomer; animal facility; autocrine; base; bone morphogenetic protein 2; cardiovascular risk factor; cell growth; cholinergic; concept; cytokine; db/db mouse; design; desire; diabetic; effectiveness research; experience; genetic analysis; genetic epidemiology; genetic linkage analysis; genome wide association study; hemodynamics; human disease; human study; human subject; improved; in vivo; interest; kidney cell; kidney cortex; liver transplantation; macroalbuminuria; malignant breast neoplasm; man; member; mesangial cell; migration; mortality; mouse model; multidisciplinary; nephrogenesis; novel; post-doctoral training; prevent; programs; receptor; response; response to injury; sex; slit diaphragm; structural biology; success; tool; trait; transcription factor; transmission process; 1-Phosphatidylinositol 3-Kinase; 15q; Address; Adult; Affect; Age; Albumins; Albuminuria; American; Angiotensin II; Angiotensins; Animal Model; Animals; Apoptosis; Applications Grants; Applied Research; Arachidonic Acids; Area; Arts; Attenuated; BRCA1 gene; Basic Science; Binding; Binding Proteins; Biochemical; Biochemical Genetics; Biochemistry; Biological Models; Biomedical Research; Biotechnology; Blood Platelets; Blood Vessels; Blood flow; Bos taurus; Bradykinin; Calcineurin; Candidate Disease Gene; Capillary Permeability; Cardiovascular Diseases; Cattle; Cell Cycle; Cell Cycle Proteins; Cell Differentiation process; Cell Proliferation; Cell physiology; Cells; Cellular biology; Cholinergic Agents; Chromosome Mapping; Chromosome Segregation; Chromosomes; Chromosomes, Human, Pair 15; Chronic; Clinical; Clinical Research; Collaborations; Colon Carcinoma; Communities; Complement; Consult; Core Facility; Country; Creatinine; Cross-Sectional Studies; Cutaneous; DNA Sequence; DNA biosynthesis; DNA chemical synthesis; Data; Death Rate; Detection; Development; Diabetes Mellitus; Diabetic Nephropathy; Diagnosis; Direct Costs; Discipline; Disease; Distal; Dorsal; E 10; Effectiveness; End stage renal failure; Endothelial Cells; Endothelin B Receptor; Enrollment; Environment; Enzyme Gene; Epidemiologist; Epithelial Cells; Equilibrium; Eukaryotic Initiation Factor-4E; Event; Exercise; Extracellular Matrix; Faculty; Family; Fellowship; Fingers; Forearm; Fostering; Foundations; Funding; Future; Gene Mutation; General Anesthesia; General Population; Genes; Genetic; Genetic Determinism; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Variation; Genotype; Glomerular Capillary; Glomerulonephritis; Goals; Grant; Growth Factor; Growth Factor Receptors; Hand; Health Sciences; Heat Stress Disorders; Heat-Shock Response; Hereditary Disease; Histology; Hormonal; Human; Human Genetics; Hybrids; Hyperemia; Hyperglycemia; Hyperinsulinism; Hypertension; Hypertrophy; IGF1 gene; Immigration; Individual; Infusion procedures; Injury; Institutes; Institution; Instruction; Insulin; Insulin Receptor; Insulin-Like Growth Factor I; International; Investigation; Ion Channel; Iontophoresis; Joints; Journals; Kidney; Kidney Diseases; Laboratories; Laminin; Lead; Leucine; Link; Linkage Disequilibrium; Location; Longitudinal Studies; Malignant Neoplasms; Manuscripts; Maps; Measurement; Mediating; Medicine; Membrane Proteins; Mesenchymal; Metabolic; Mexican Americans; Microalbuminuria; Mitochondria; Mitosis; Modeling; Molecular; Molecular Chaperones; Molecular Genetics; Morbidity - disease rate; Morphology; Motivation; Mus; Mutation; N(delta)-acetylornithine, -isomer; N-dodecanoylglutamic acid, -isomer, sodium salt; Names; Nature; Nephrology; Nerve; Non-Insulin-Dependent Diabetes Mellitus; Nuclear Protein; Nuclear Proteins; Numbers; Oxidation-Reduction; Papio; Participant; Pathogenesis; Pathology; Pathway interactions; Patients; Peer Review; Peptidyl-Dipeptidase A; Peripheral; Personal Satisfaction; Phenotype; Philadelphia; Phosphatidylinositols; Phosphorylation; Phosphotransferases; Physicians; Physiology; Platelet Factor 4; Platelet-Derived Growth Factor; Platelet-Derived Growth Factor Receptor; Play; Polycystic Kidney Diseases; Predisposition; Preparation; Prevalence; Prevention; Primates; Principal Investigator; Process; Prostate; Protein-Serine-Threonine Kinases; Proteins; Proteinuria; Proto-Oncogene Proteins c-akt; Protocols documentation; Proximal Kidney Tubules; Publications; Publishing; Purpose; Quantitative Trait Loci; Race; Rate; Rattus; Recording of previous events; Recruitment Activity; Reflex control; Regulation; Renin; Renin-Angiotensin System; Research; Research Activity; Research Personnel; Research Project Grants; Research Subjects; Research Training; Resources; Rest; Retinoblastoma; Retinoblastoma Protein; Rice; Risk; Role; Science; Scientist; Secondary to; Serine; Services; Severities; Sex Characteristics; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Single Nucleotide Polymorphism; Skin; Skin Temperature; Snake Venoms; Societies; Sports Medicine; Staging; Stimulation of Cell Proliferation; Stimulus; Structural Protein; Study Subject; Supervision; System; Temperature; Testing; Texas; Textbooks; Thinking; Thrombin; Tight Junctions; Time; Training; Transforming Growth Factor beta; Transgenes; Transgenic Animals; Transgenic Organisms; Translations; Trimeresurus; Tubular formation; United States; United States Department of Veterans Affairs; United States National Institutes of Health; Universities; Urine; Ursidae Family; VDAC1 gene; Variant; Vascular Endothelial Growth Factor Receptor; Vasodilation; Vasodilator Agents; Visit; Work; Yeasts; adipocyte differentiation; alpha-difluoromethyl-DOPA, -isomer; alpha-methylornithine dihydrochloride, -isomer; animal facility; autocrine; base; bone morphogenetic protein 2; cardiovascular risk factor; cell growth; cholinergic; concept; cytokine; db/db mouse; design; desire; diabetic; effectiveness research; experience; genetic analysis; genetic epidemiology; genetic linkage analysis; genome wide association study; hemodynamics; human disease; human study; human subject; improved; in vivo; interest; kidney cell; kidney cortex; liver transplantation; macroalbuminuria; malignant breast neoplasm; man; member; mesangial cell; migration; mortality; mouse model; multidisciplinary; nephrogenesis; novel; post-doctoral training; prevent; programs; receptor; response; response to injury; sex; slit diaphragm; structural biology; success; tool; trait; transcription factor; transmission process

DESCRIPTION (provided by applicant) This is a revised application in response to RFA: DK-02-028 for the establishment of the George M. O'Brien Kidney Research Center at the University of Texas Health Science Center. The application focuses on the response of the kidney to diverse forms of injury with the goal of identifying genetic factors and mechanisms of development of diabetic and polycystic kidney disease. The Center is composed of three scientific projects, one core, and three feasibility/developmental projects that bring together scientists from the Departments of Medicine, Cell and Structural Biology, Physiology, and the Institute of Biotechnology at the University of Texas Health Science Center at San Antonio and the Department of Genetics at the Southwest Foundation for Biomedical Research. In Project 1, Dr. Abboud will investigate a positional candidate gene, tight junction protein-1 (TJP-1) to identify DNA sequence variants that are responsible for the linkage to albuminura. In Project 2, Dr. Kasinath will explore the signaling mechanisms by which hyperinsulinemia results in protein translation and matrix accumulation in the db/db mouse model of type II diabetes. In Project 3, Dr. Chen, will explore the role of nekl kinase in the pathogenesis of polycystic kidney disease. In Project 4 (Development/Feasibility) Dr. Pergola explores microcirculatory responses to manipulations of the renin-angiotensin system as a potential tool to identify patients at risks for development of diabetic nephropathy. In Project 5 (Development/Feasibility), Dr. Gooch will study the role of calcineurin in IGF1 and TGFbeta signaling as it pertains to diabetic nephropathy. Project 6 (Development/Feasibility), Dr. Rincon-Choles will characterize kidney phenotype and identify quantitative trait loci influencing diabetic nephropathy in a pedigreed and genotyped colony of baboons with type II diabetes. Four of the six projects will utilize the services of the Morphology Core, and three of the six projects will utilize the Transgenic Core Facility. It is anticipated that the studies will advance the understanding of genetic, biochemical, and cellular factors that modulate renal response to injury.

描述（由申请人提供） 这是对RFA：DK-02-028的修订申请，用于在德克萨斯大学健康科学中心建立George M. O'Brien肾脏研究中心。该应用的重点是肾脏对各种形式的损伤的反应，目的是确定遗传因素和糖尿病和多囊肾脏疾病的发展机制。该中心由三个科学项目，一个核心和三个可行性/发展项目组成，这些项目将医学，细胞和结构生物学，生理学部门以及得克萨斯州圣安东尼奥大学健康科学中心和西南生物医学研究基金会的遗传学系的科学家组成。在项目1中，Abboud博士将研究一个位置候选基因，紧密的连接蛋白-1（TJP-1），以识别负责与白蛋白链接链接的DNA序列变体。在项目2中，Kasinath博士将探讨高胰岛素血症导致蛋白质翻译和基质在II型糖尿病的DB/DB小鼠模型中积累的信号传导机制。在项目3中，Chen博士将探讨NEKL激酶在多囊肾病发病机理中的作用。在项目4（发展/可行性）中，Pergola博士探讨了对肾素 - 血管紧张素系统操纵的微循环反应，作为识别有糖尿病性肾病风险的患者的潜在工具。在项目5（开发/可行性）中，Gooch博士将研究钙调神经酶在IGF1和TGFBETA信号中的作用，因为它与糖尿病性肾病有关。项目6（开发/可行性），林肯 - 核博士将表征肾脏表型，并鉴定出影响II型糖尿病的狒狒的幼稚和基因型菌落中影响糖尿病肾病的定量性状基因座。六个项目中有四个将利用形态核心的服务，六个项目中的三个将利用转基因核心设施。预计研究将提高对调节肾脏对损伤反应的遗传，生化和细胞因子的理解。