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      Renalase's Expression and Distribution in Renal Tissue and Cells

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          Abstract

          To study renalase's expression and distribution in renal tissues and cells, renalase coded DNA vaccine was constructed, and anti-renalase monoclonal antibodies were produced using DNA immunization and hybridoma technique, followed by further investigation with immunological testing and western blotting to detect the expression and distribution of renalase among the renal tissue and cells. Anti-renalase monoclonal antibodies were successfully prepared by using DNA immunization technique. Further studies with anti-renalase monoclonal antibody showed that renalase expressed in glomeruli, tubule, mesangial cells, podocytes, renal tubule epithelial cells and its cells supernatant. Renalase is wildly expressed in kidney, including glomeruli, tubule, mesangial cells, podocytes and tubule epithelial cells, and may be secreted by tubule epithelial cells primarily.

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          Renalase is a novel, soluble monoamine oxidase that regulates cardiac function and blood pressure.

          The kidney not only regulates fluid and electrolyte balance but also functions as an endocrine organ. For instance, it is the major source of circulating erythropoietin and renin. Despite currently available therapies, there is a marked increase in cardiovascular morbidity and mortality among patients suffering from end-stage renal disease. We hypothesized that the current understanding of the endocrine function of the kidney was incomplete and that the organ might secrete additional proteins with important biological roles. Here we report the identification of a novel flavin adenine dinucleotide-dependent amine oxidase (renalase) that is secreted into the blood by the kidney and metabolizes catecholamines in vitro (renalase metabolizes dopamine most efficiently, followed by epinephrine, and then norepinephrine). In humans, renalase gene expression is highest in the kidney but is also detectable in the heart, skeletal muscle, and the small intestine. The plasma concentration of renalase is markedly reduced in patients with end-stage renal disease, as compared with healthy subjects. Renalase infusion in rats caused a decrease in cardiac contractility, heart rate, and blood pressure and prevented a compensatory increase in peripheral vascular tone. These results identify renalase as what we believe to be a novel amine oxidase that is secreted by the kidney, circulates in blood, and modulates cardiac function and systemic blood pressure.
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            Sympathetic activation in chronic renal failure.

            The potential involvement of sympathetic overactivity has been neglected in this population despite accumulating experimental and clinical evidence suggesting a crucial role of sympathetic activation for both progression of renal failure and the high rate of cardiovascular events in patients with chronic kidney disease. The contribution of sympathetic neural mechanisms to the occurrence of cardiac arrhythmias, the development of hypertension, and the progression of heart failure are well established; however, the exact mechanisms contributing to heightened sympathetic tone in patients with chronic kidney disease are unclear. This review analyses potential mechanisms underlying sympathetic activation in chronic kidney disease, the range of adverse consequences associated with this activation, and potential therapeutic implications resulting from this relationship.
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              Sympathetic hyperactivity in chronic kidney disease: pathogenesis, clinical relevance, and treatment.

              Cardiovascular morbidity and mortality importantly influence live expectancy of patients with chronic renal disease (CKD). Traditional risk factors are usually present, but several other factors have recently been identified. There is now evidence that CKD is often characterized by an activated sympathetic nervous system. This may contribute to the pathogenesis of renal hypertension, but it may also adversely affect prognosis independently of its effect on blood pressure. The purpose of this review is to summarize available knowledge on the role of the sympathetic nervous system in the pathogenesis of renal hypertension, its clinical relevance, and the consequences of this knowledge for the choice of treatment.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                3 October 2012
                : 7
                : 10
                : e46442
                Affiliations
                [1 ]Department of Nephrology and Rheumatology, Shanghai Sixth People's Hospital affiliated to Shanghai Jiaotong University, Shanghai, China
                [2 ]The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Australia
                [3 ]Department of Pathology, Shanghai Medical College, Fudan Univesity, Shanghai, China
                University of Louisville, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: FW TX. Performed the experiments: FW TX JL MB RH Z. Zhao ST Z. Zhang. Analyzed the data: FW TX. Contributed reagents/materials/analysis tools: FW Z. Zhang NW. Wrote the paper: FW TX.

                Article
                PONE-D-12-21726
                10.1371/journal.pone.0046442
                3463591
                23056310
                90d856a6-2e96-4752-b45a-45ea4f1743d3
                Copyright @ 2012

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 18 July 2012
                : 30 August 2012
                Page count
                Pages: 6
                Funding
                The research is supported by grant 81100528 from the Project of National Nature Science Foundation of China, Program for Excellent Young Talents of Shanghai Sixth People's Hospital (1402), Shanghai Sixth People's Hospital Consortium Subject (1423), and Shanghai Committee of Science and Technology Research Project (114119a6100). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Anatomy and Physiology
                Renal System
                Biochemistry
                Nucleic Acids
                DNA
                Immunology
                Model Organisms
                Animal Models
                Mouse
                Molecular Cell Biology
                Nucleic Acids
                DNA
                Medicine
                Cardiovascular
                Hypertension
                Nephrology
                Chronic Kidney Disease
                Hypertension

                Uncategorized
                Uncategorized

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