Dhas Yogita, Arshad Numair, Biswas Nupur, Jones Lawrence D, Ashili Shashaanka
Rhenix Lifesciences, Hyderabad 500038, India.
CureScience, 5820 Oberlin Dr 202, San Diego, CA 92121, USA.
Biomedicines. 2023 Sep 20;11(9):2583. doi: 10.3390/biomedicines11092583.
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.
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。
