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糖尿病肾病中MicroRNA-21沉默:治疗策略的见解

MicroRNA-21 Silencing in Diabetic Nephropathy: Insights on Therapeutic Strategies.

作者信息

Dhas Yogita, Arshad Numair, Biswas Nupur, Jones Lawrence D, Ashili Shashaanka

机构信息

Rhenix Lifesciences, Hyderabad 500038, India.

CureScience, 5820 Oberlin Dr 202, San Diego, CA 92121, USA.

出版信息

Biomedicines. 2023 Sep 20;11(9):2583. doi: 10.3390/biomedicines11092583.

Abstract

In diabetes, possibly the most significant site of microvascular damage is the kidney. Due to diabetes and/or other co-morbidities, such as hypertension and age-related nephron loss, a significant number of people with diabetes suffer from kidney diseases. Improved diabetic care can reduce the prevalence of diabetic nephropathy (DN); however, innovative treatment approaches are still required. MicroRNA-21 (miR-21) is one of the most studied multipotent microRNAs (miRNAs), and it has been linked to renal fibrosis and exhibits significantly altered expression in DN. Targeting miR-21 offers an advantage in DN. Currently, miR-21 is being pharmacologically silenced through various methods, all of which are in early development. In this review, we summarize the role of miR-21 in the molecular pathogenesis of DN and several therapeutic strategies to use miR-21 as a therapeutic target in DN. The existing experimental interventions offer a way to rectify the lower miRNA levels as well as to reduce the higher levels. Synthetic miRNAs also referred to as miR-mimics, can compensate for abnormally low miRNA levels. Furthermore, strategies like oligonucleotides can be used to alter the miRNA levels. It is reasonable to target miR-21 for improved results because it directly contributes to the pathological processes of kidney diseases, including DN.

摘要

在糖尿病中,微血管损伤最显著的部位可能是肾脏。由于糖尿病和/或其他合并症,如高血压和与年龄相关的肾单位丢失,大量糖尿病患者患有肾脏疾病。改善糖尿病护理可降低糖尿病肾病(DN)的患病率;然而,仍需要创新的治疗方法。微小RNA-21(miR-21)是研究最多的多能微小RNA(miRNA)之一,它与肾纤维化有关,并且在DN中表现出显著改变的表达。靶向miR-21在DN中具有优势。目前,正在通过各种方法对miR-21进行药理学沉默,所有这些方法都处于早期开发阶段。在本综述中,我们总结了miR-21在DN分子发病机制中的作用以及几种将miR-21用作DN治疗靶点的治疗策略。现有的实验干预措施提供了一种纠正较低miRNA水平以及降低较高水平的方法。合成miRNA也称为miR模拟物,可以补偿异常低的miRNA水平。此外,像寡核苷酸这样的策略可用于改变miRNA水平。将miR-21作为靶点以获得更好的结果是合理的,因为它直接促成包括DN在内的肾脏疾病的病理过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4eb1/10527294/eaf1400752d0/biomedicines-11-02583-g001.jpg

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