摘要
简介:代谢综合征(MS)是随着身体质量指数(BMI)和年龄的增加而迅速发展的全球社会经济问题。它是由血脂异常,胰岛素抵抗,瘦素抵抗,脂联素降低,葡萄糖耐受不良,高血糖和高血压等危险因素组成的联盟。这些因素共同加速了2型糖尿病,心血管疾病,中风以及乳腺癌,肝胰腺癌和结肠癌等某些癌症的发病。细胞外基质(ECM)和基底膜重塑在MS发病过程中起着核心作用,因为它们调节多种细胞功能,包括增殖,分化和迁移。因此,重塑ECM的蛋白质的调节为大多数MS提供了有希望的治疗机会。基质金属蛋白酶(MMPs)是锌依赖性内肽酶家族,是参与ECM重塑的主要酶。新兴的研究报道了在MS期间MMP和TIMP的组织抑制剂水平的改变。一些药物MMP抑制剂正在开发中,但它们尚未被认可用于临床应用。 结论:近来,由于其操纵基因表达的能力,微RNA(〜2123个核苷酸,小的非编码,内源性,单链RNA)已经成为治疗性干预的一类有前景的实体。通过小的非编码RNA调节MMPs靶向ECM重塑的组合策略在癌症和心血管疾病的临床前研究中产生令人鼓舞的结果。这篇综述有助于深入了解microRNA作为MS调节剂的作用,以及作为与MMPs直接和间接相互作用的治疗工具的潜力。
关键词: 代谢综合征,MMP,TIMP,细胞外基质,microRNA,高血压。
Current Gene Therapy
Title:MicroRNA-mediated MMP Regulation: Current Diagnostic and Therapeutic Strategies for Metabolic Syndrome
Volume: 17 Issue: 3
关键词: 代谢综合征,MMP,TIMP,细胞外基质,microRNA,高血压。
摘要: Introduction: Metabolic Syndrome (MS) is a global socioeconomic problem rapidly progressing in accordance with increasing Body Mass Index (BMI) and age. It is a consortium of risk factors, such as dyslipidaemia, insulin resistance, leptin resistance, reduced adiponectin, glucose intolerance, hyperglycemia, and hypertension. Collectively, these factors accelerate the onset of type 2 diabetes mellitus, cardiovascular disease, stroke, and certain cancers such as breast, liver pancreatic, and colon cancer. Extracellular Matrix (ECM) and basement membrane remodeling play a central role during pathogenesis of MS as they regulate diverse cell functions including proliferation, differentiation, and migration. Therefore, regulation of proteins that remodel the ECM offers promising therapeutic opportunities for most of the MS. Matrix Metalloproteinases (MMPs), a family of zinc dependent endopeptidases, are the main enzymes involved in ECM remodeling. Emerging studies have reported altered levels of MMPs and the Tissue Inhibitors of Metalloproteinases (TIMPs) during MS. A number of pharmaceutical MMP inhibitors are being developed, but they have yet to be recognized for clinical applications.
Conclusion: Recently, microRNAs (~21–23-nucleotide, small non-coding, endogenous, single-stranded RNAs) have emerged as a class of promising entities for therapeutic intervention due to their ability to manipulate gene expression. The combined strategy of targeting ECM remodeling through regulation of MMPs by small non-coding RNA has produced encouraging results in pre-clinical studies for cancer and cardiovascular diseases. This review serves to provide insight into the role of microRNAs as modulators of MS and their potential as therapeutics tool through direct and indirect interactions with the MMPs.
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MicroRNA-mediated MMP Regulation: Current Diagnostic and Therapeutic Strategies for Metabolic Syndrome, Current Gene Therapy 2017; 17 (3) . https://dx.doi.org/10.2174/1566523217666170707100026
DOI https://dx.doi.org/10.2174/1566523217666170707100026 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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