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药物调控内皮祖细胞对糖尿病及糖尿病相关疾病的多重治疗作用。

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

机构信息

Molecular Neuroscience and Functional Genomics Laboratory, Department of Biotechnology, DTU, Delhi, India.

出版信息

J Transl Med. 2017 Aug 31;15(1):185. doi: 10.1186/s12967-017-1280-y.

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.

摘要

背景

已有研究报道,糖尿病(DM)患者及其他糖尿病相关疾病存在内皮祖细胞(EPC)计数减少的情况。EPC 是一种循环的骨髓来源细胞群,似乎参与血管发生、血管生成和损伤修复。这些 EPC 可能逆转糖尿病状态下造成的损伤。我们旨在确定几种现有的药物和信号分子,通过动员和增加 EPC 的数量和功能,来减轻或改善糖尿病的状况。

主要内容

越来越多的证据表明,EPC 表型和功能的失调可能归因于 DM 患者中的几种信号分子和细胞因子。高血糖本身通过 eNOS 和 NOX 产生过多的活性氧(ROS),可以诱导糖尿病中基因表达和细胞行为的改变。此外,有报道称,EPC 端粒通过增加氧化 DNA 损伤而缩短,这可能在糖尿病患者的冠状动脉疾病发病机制中发挥重要作用。在这篇综述中,讨论了不同来源的不同类型的 EPC 及其表面标志物。还讨论了通过使用现有的和新型药物动员糖尿病状态下数量减少和固定的 EPC 以达到治疗目的。因此,综述了所有已报道的靶向同一途径的药物的证据清单,这些药物会影响糖尿病中 EPC 的数量和功能。此外,我们强调了蛋白质通过多态性和抑制剂研究在糖尿病中是至关重要的。最终,为了理解疾病和正常状态下潜在的复杂信号之谜,我们以清晰的图示解释了收集到的数据中糖尿病患者和正常患者的信号通路。

结论

最后,我们得出结论,即 eNOS-二甲双胍-Hsp90 信号及其对控制 EPC 的补救作用,可改善糖尿病状况,延缓糖尿病相关并发症的发生。总的来说,该综述全面概述了新型和现有药物对糖尿病及相关疾病中 EPC 的精细治疗作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de9e/5580204/dc4bd3b78b01/12967_2017_1280_Fig1_HTML.jpg

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