Paris Cardiovascular Research Center - PARCC, Inserm, Université Paris Cité, Paris, France.
Service de Néphrologie et Transplantation Adulte, Hôpital Necker-Enfants Malades, Université Paris Cité, Assistance Publique-Hôpitaux de Paris, Paris, France.
Nat Rev Nephrol. 2022 Oct;18(10):643-662. doi: 10.1038/s41581-022-00608-6. Epub 2022 Aug 16.
MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by degrading or repressing the translation of their target messenger RNAs. As miRNAs are critical regulators of cellular homeostasis, their dysregulation is a crucial component of cell and organ injury. A substantial body of evidence indicates that miRNAs are involved in the pathophysiology of acute kidney injury (AKI), chronic kidney disease and allograft damage. Different subsets of miRNAs are dysregulated during AKI, chronic kidney disease and allograft rejection, which could reflect differences in the physiopathology of these conditions. miRNAs that have been investigated in AKI include miR-21, which has an anti-apoptotic role, and miR-214 and miR-668, which regulate mitochondrial dynamics. Various miRNAs are downregulated in diabetic kidney disease, including the miR-30 family and miR-146a, which protect against inflammation and fibrosis. Other miRNAs such as miR-193 and miR-92a induce podocyte dedifferentiation in glomerulonephritis. In transplantation, miRNAs have been implicated in allograft rejection and injury. Further work is needed to identify and validate miRNAs as biomarkers of graft function and of kidney disease development and progression. Use of combinations of miRNAs together with other molecular markers could potentially improve diagnostic or predictive power and facilitate clinical translation. In addition, targeting specific miRNAs at different stages of disease could be a promising therapeutic strategy.
微小 RNA(miRNAs)是一种小的非编码 RNA,可以通过降解或抑制其靶信使 RNA 的翻译来调节基因表达。由于 miRNAs 是细胞内稳态的关键调节剂,它们的失调是细胞和器官损伤的重要组成部分。大量证据表明,miRNAs 参与了急性肾损伤(AKI)、慢性肾脏病和同种异体移植损伤的病理生理学过程。不同亚群的 miRNAs 在 AKI、慢性肾脏病和同种异体移植排斥中失调,这可能反映了这些疾病在病理生理学方面的差异。在 AKI 中研究过的 miRNAs 包括具有抗凋亡作用的 miR-21,以及调节线粒体动力学的 miR-214 和 miR-668。在糖尿病肾病中,许多 miRNAs 下调,包括 miR-30 家族和 miR-146a,它们可以防止炎症和纤维化。其他 miRNAs,如 miR-193 和 miR-92a,在肾小球肾炎中诱导足细胞去分化。在移植中,miRNAs 与同种异体移植排斥和损伤有关。需要进一步的工作来鉴定和验证 miRNAs 作为移植物功能和肾脏疾病发展和进展的生物标志物。miRNAs 与其他分子标志物的联合使用可能会提高诊断或预测能力,并促进临床转化。此外,针对疾病不同阶段的特定 miRNAs 可能是一种很有前途的治疗策略。