Department of Diabetes, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
Free Radic Biol Med. 2013 Sep;64:85-94. doi: 10.1016/j.freeradbiomed.2013.06.009. Epub 2013 Jun 12.
The incidence of diabetes is escalating worldwide and, consequently, this has become a major health care problem. Moreover, both type 1 and type 2 diabetes are associated with significantly accelerated rates of microvascular complications, including retinopathy, nephropathy, and neuropathy, as well as macrovascular complications such as atherosclerotic cardiovascular and hypertensive diseases. Key factors have been implicated in leading to these complications, including hyperglycemia, insulin resistance, dyslipidemia, advanced glycation end products, growth factors, inflammatory cytokines/chemokines, and related increases in cellular oxidant stress (including mitochondrial) and endoplasmic reticulum stress. However, the molecular mechanisms underlying the high incidence of diabetic complications, which often progress despite glycemic control, are still not fully understood. MicroRNAs (miRNAs) are short noncoding RNAs that have elicited immense interest in recent years. They repress target gene expression via posttranscriptional mechanisms and have diverse cellular and biological functions. Herein, we discuss the role of miRNAs in the pathobiology of various diabetic complications, their involvement in oxidant stress, and also the potential use of differentially expressed miRNAs as novel diagnostic biomarkers and therapeutic targets.
糖尿病的发病率在全球范围内不断上升,因此这已成为一个主要的医疗保健问题。此外,1 型和 2 型糖尿病都与微血管并发症的发生率显著加快有关,包括视网膜病变、肾病和神经病变,以及大血管并发症,如动脉粥样硬化性心血管疾病和高血压疾病。导致这些并发症的关键因素包括高血糖、胰岛素抵抗、血脂异常、糖基化终产物、生长因子、炎症细胞因子/趋化因子,以及相关的细胞氧化剂应激(包括线粒体)和内质网应激增加。然而,尽管血糖控制良好,糖尿病并发症高发的分子机制仍不完全清楚。微小 RNA(miRNA)是近年来引起广泛关注的短非编码 RNA。它们通过转录后机制抑制靶基因的表达,并具有多种细胞和生物学功能。本文讨论了 miRNA 在各种糖尿病并发症的病理生物学中的作用,它们在氧化剂应激中的参与,以及差异表达的 miRNA 作为新型诊断生物标志物和治疗靶点的潜在用途。