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      Multiple therapeutic effect of endothelial progenitor cell regulated by drugs in diabetes and diabetes related disorder

      review-article
      , ,
      Journal of Translational Medicine
      BioMed Central
      Diabetes, EPC, eNOS, Metformin, ROS, NOX

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          Abstract

          Background

          Reduced levels of endothelial progenitor cells (EPCs) counts have been reported in diabetic mellitus (DM) patients and other diabetes-related disorder. EPCs are a circulating, bone marrow-derived cell population that appears to participate in vasculogenesis, angiogenesis and damage repair. These EPC may revert the damage caused in diabetic condition. We aim to identify several existing drugs and signaling molecule, which could alleviate or improve the diabetes condition via mobilizing and increasing EPC number as well as function.

          Main body

          Accumulated evidence suggests that dysregulation of EPC phenotype and function may be attributed to several signaling molecules and cytokines in DM patients. Hyperglycemia alone, through the overproduction of reactive oxygen species (ROS) via eNOS and NOX, can induce changes in gene expression and cellular behavior in diabetes. Furthermore, reports suggest that EPC telomere shortening via increased oxidative DNA damage may play an important role in the pathogenesis of coronary artery disease in diabetic patients. In this review, different type of EPC derived from different sources has been discussed along with cell-surface marker. The reduced number and immobilized EPC in diabetic condition have been mobilized for the therapeutic purpose via use of existing, and novel drugs have been discussed. Hence, evidence list of all types of drugs that have been reported to target the same pathway which affect EPC number and function in diabetes has been reviewed. Additionally, we highlight that proteins are critical in diabetes via polymorphism and inhibitor studies. Ultimately, a lucid pictorial explanation of diabetic and normal patient signaling pathways of the collected data have been presented in order to understand the complex signaling mystery underlying in the diseased and normal condition.

          Conclusion

          Finally, we conclude on eNOS-metformin-HSp90 signaling and its remedial effect for controlling the EPC to improve the diabetic condition for delaying diabetes-related complication. Altogether, the review gives a holistic overview about the elaborate therapeutic effect of EPC regulated by novel and existing drugs in diabetes and diabetes-related disorder.

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          Most cited references112

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          Extension of life-span by introduction of telomerase into normal human cells.

          Normal human cells undergo a finite number of cell divisions and ultimately enter a nondividing state called replicative senescence. It has been proposed that telomere shortening is the molecular clock that triggers senescence. To test this hypothesis, two telomerase-negative normal human cell types, retinal pigment epithelial cells and foreskin fibroblasts, were transfected with vectors encoding the human telomerase catalytic subunit. In contrast to telomerase-negative control clones, which exhibited telomere shortening and senescence, telomerase-expressing clones had elongated telomeres, divided vigorously, and showed reduced straining for beta-galactosidase, a biomarker for senescence. Notably, the telomerase-expressing clones have a normal karyotype and have already exceeded their normal life-span by at least 20 doublings, thus establishing a causal relationship between telomere shortening and in vitro cellular senescence. The ability to maintain normal human cells in a phenotypically youthful state could have important applications in research and medicine.
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            Telomeres and human disease: ageing, cancer and beyond.

            Telomere length and telomerase activity are important factors in the pathobiology of human disease. Age-related diseases and premature ageing syndromes are characterized by short telomeres, which can compromise cell viability, whereas tumour cells can prevent telomere loss by aberrantly upregulating telomerase. Altered functioning of both telomerase and telomere-interacting proteins is present in some human premature ageing syndromes and in cancer, and recent findings indicate that alterations that affect telomeres at the level of chromatin structure might also have a role in human disease. These findings have inspired a number of potential therapeutic strategies that are based on telomerase and telomeres.
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              Telomere shortening and tumor formation by mouse cells lacking telomerase RNA.

              To examine the role of telomerase in normal and neoplastic growth, the telomerase RNA component (mTR) was deleted from the mouse germline. mTR-/- mice lacked detectable telomerase activity yet were viable for the six generations analyzed. Telomerase-deficient cells could be immortalized in culture, transformed by viral oncogenes, and generated tumors in nude mice following transformation. Telomeres were shown to shorten at a rate of 4.8+/-2.4 kb per mTR-/- generation. Cells from the fourth mTR-/- generation onward possessed chromosome ends lacking detectable telomere repeats, aneuploidy, and chromosomal abnormalities, including end-to-end fusions. These results indicate that telomerase is essential for telomere length maintenance but is not required for establishment of cell lines, oncogenic transformation, or tumor formation in mice.
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                Author and article information

                Contributors
                +91-9818898638 , rashmiambasta@gmail.com , rashmiambasta@dce.ac.in
                harleen521@gmail.com
                kpravir@gmail.com
                Journal
                J Transl Med
                J Transl Med
                Journal of Translational Medicine
                BioMed Central (London )
                1479-5876
                31 August 2017
                31 August 2017
                2017
                : 15
                : 185
                Affiliations
                ISNI 0000 0001 0674 5044, GRID grid.440678.9, Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, , DTU, ; Delhi, India
                Author information
                http://orcid.org/0000-0002-8874-7752
                http://orcid.org/0000-0001-7444-2344
                Article
                1280
                10.1186/s12967-017-1280-y
                5580204
                28859673
                de65e511-0eff-4745-9c71-e4de34abccd9
                © The Author(s) 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 4 May 2017
                : 12 August 2017
                Funding
                Funded by: CSIR
                Award ID: CSIR-SRA
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2017

                Medicine
                diabetes,epc,enos,metformin,ros,nox
                Medicine
                diabetes, epc, enos, metformin, ros, nox

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