MicroRNAs as Biomarkers and Therapeutic Targets in Inflammation- and Ischemia-Reperfusion-Related Acute Renal Injury

Abstract

Acute kidney injury (AKI), caused mainly by ischemia-reperfusion, sepsis, or nephrotoxins (such as contrast medium), is identified by an abrupt decline in kidney function and is associated with high morbidity and mortality. Despite decades of efforts, the pathogenesis of AKI remains poorly understood, and effective therapies are lacking. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the posttranscriptional level to control cell differentiation, development, and homeostasis. Additionally, extracellular miRNAs might mediate cell–cell communication during various physiological and pathological processes. Recently, mounting evidence indicates that miRNAs play a role in the pathogenesis of AKI. Moreover, emerging research suggests that because of their remarkable stability in body fluids, microRNAs can potentially serve as novel diagnostic biomarkers of AKI. Of note, our previous finding that miR-494 is rapidly elevated in urine but not in serum provides insight into the ultimate role of urine miRNAs in AKI. Additionally, exosomal miRNAs derived from stem cells, known as the stem cell secretome, might be a potential innovative therapeutic strategy for AKI. This review aims to provide new data obtained in this field of research. It is hoped that new studies on this topic will not only generate new insights into the pathophysiology of urine miRNAs in AKI but also might lead to the precise management of this fatal disease.

Toll-Like Receptors in Acute Kidney Injury

“…These novel biomarkers are related with pathological processes involved in AKI development, such as inflammation, oxidative stress and renal cells death [19,20]. Furthermore, current studies support the potential value of circulating and urinary miRNAs as novel AKI biomarkers e.g., miR-21, miR-30a-e and miR-494, among others [18,21,22].…”

MicroRNAs as Biomarkers for Nephrotic Syndrome

“…miRNAs have been widely reported as promising biomarkers for many diseases. In fact, they have been shown as non-invasive biomarkers in multiple diseases including cancers and renal diseases [ 14 , 15 , 16 , 17 ]. Because miRNAs may directly be associated with pathogenesis of some types of NS, to analyze miRNA profiles in NS patients is not only for the diagnosis for the specific diseases, but also for understanding and elucidating the disease pathogenesis and even for establishing novel therapies.…”

MiR-124 Negatively Regulated PARP1 to Alleviate Renal Ischemia-reperfusion Injury by Inhibiting TNFα/RIP1/RIP3 Pathway

“…Renal ischemia-reperfusion injury is the main cause of acute renal injury 24 and an unavoidable problem in renal transplantation 25 . Recent studies have shown that some miRNAs are extensively involved in several organs and tissues of IRI 8 , 26 . MiR-124 has been reported to participate extensively in the pathophysiology of ischemic stroke, functioning as a protective role against cerebral ischemia-reperfusion injury 27 , 28 .…”

“…MicroRNAs are highly conserved small RNA molecules of 21-25 nucleotides, which have been reported to be associated with renal IRI 8 . For example, miR-687 was markedly upregulated during renal ischemia-reperfusion injury in mice and cell models 9 .…”