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      Vitamin D Receptor: A Novel Therapeutic Target for Kidney Diseases

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          Abstract

          Background:

          Kidney disease is a serious problem that adversely affects human health, but critical knowledge is lacking on how to effectively treat established chronic kidney disease. Mounting evidence from animal and clinical studies has suggested that Vitamin D Re-ceptor (VDR) activation has beneficial effects on various renal diseases.

          Methods:

          A structured search of published research literature regarding VDR structure and function, VDR in various renal diseases (e.g., IgA nephropathy, idiopathic nephrotic syndrome, renal cell carcinoma, diabetic nephropathy, lupus nephritis) and therapies targeting VDR was performed for several databases.

          Result:

          Included in this study are the results from 177 published research articles. Evidence from these papers indicates that VDR activation is involved in the protection against renal inju-ry in kidney diseases by a variety of mechanisms, including suppression of RAS activation, an-ti-inflammation, inhibiting renal fibrogenesis, restoring mitochondrial function, suppression of autoimmunity and renal cell apoptosis.

          Conclusion:

          VDR offers an attractive druggable target for renal diseases. Increasing our under-standing of VDR in the kidney is a fertile area of research and may provide effective weapons in the fight against kidney diseases

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          Most cited references161

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          Mitochondrial energetics in the kidney

          Mitochondria provide the kidney with energy to remove waste from the blood and regulate fluid and electrolyte balance. This Review discusses how mitochondrial homeostasis is maintained, the changes in mitochondrial energetics that occur in acute kidney injury and diabetic nephropathy, and how targeting mitochondrial energetics might aid the treatment of renal disease.
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            Mechanisms of tubulointerstitial fibrosis.

            The pathologic paradigm for renal progression is advancing tubulointerstitial fibrosis. Whereas mechanisms underlying fibrogenesis have grown in scope and understanding in recent decades, effective human treatment to directly halt or even reverse fibrosis remains elusive. Here, we examine key features mediating the molecular and cellular basis of tubulointerstitial fibrosis and highlight new insights that may lead to novel therapies. How to prevent chronic kidney disease from progressing to renal failure awaits even deeper biochemical understanding.
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              A glimpse of various pathogenetic mechanisms of diabetic nephropathy.

              Diabetic nephropathy is a well-known complication of diabetes and is a leading cause of chronic renal failure in the Western world. It is characterized by the accumulation of extracellular matrix in the glomerular and tubulointerstitial compartments and by the thickening and hyalinization of intrarenal vasculature. The various cellular events and signaling pathways activated during diabetic nephropathy may be similar in different cell types. Such cellular events include excessive channeling of glucose intermediaries into various metabolic pathways with generation of advanced glycation products, activation of protein kinase C, increased expression of transforming growth factor β and GTP-binding proteins, and generation of reactive oxygen species. In addition to these metabolic and biochemical derangements, changes in the intraglomerular hemodynamics, modulated in part by local activation of the renin-angiotensin system, compound the hyperglycemia-induced injury. Events involving various intersecting pathways occur in most cell types of the kidney.
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                Author and article information

                Journal
                Curr Med Chem
                Curr. Med. Chem
                CMC
                Current Medicinal Chemistry
                Bentham Science Publishers
                0929-8673
                1875-533X
                August 2018
                August 2018
                : 25
                : 27
                : 3256-3271
                Affiliations
                Department of Nephrology, The Third Xiangya Hospital, Central South University , Changsha, , Hunan , China, Department of Medicine, Division of Biological Sciences, The University of Chicago , Chicago, , Illinois , USA
                Author notes
                [* ]Address correspondence to this author is at the Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, China; Tel: 86-731-88638238; E-mail: zhanghaoliaoqing@ 123456163.com
                Article
                CMC-25-3256
                10.2174/0929867325666180214122352
                6142412
                29446731
                b8b91922-f0f8-46eb-8385-491226ea9c66
                © 2018 Bentham Science Publishers

                This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

                History
                : 10 November 2017
                : 28 December 2017
                : 12 February 2018
                Categories
                Article

                Pharmaceutical chemistry
                vitamin d receptor,renal injury,renal tubular epithelial cell,chronic kidney disease,renal osteodystrophy,acute kidney injury

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