A model-specific role of microRNA-223 as a mediator of kidney injury during experimental sepsis

Abstract

Sepsis outcomes are heavily dependent on the development of septic organ injury, but no interventions exist to interrupt or reverse this process. microRNA-223 (miR-223) is known to be involved in both inflammatory gene regulation and host-pathogen interactions key to the pathogenesis of sepsis. The goal of this study was to determine the role of miR-223 as a mediator of septic kidney injury. Using miR-223 knockout mice and multiple models of experimental sepsis, we found that miR-223 differentially influences acute kidney injury (AKI) based on the model used. In the absence of miR-223, mice demonstrated exaggerated AKI in sterile models of sepsis (LPS injection) and attenuated AKI in a live-infection model of sepsis (cecal ligation and puncture). We demonstrated that miR-223 expression is induced in kidney homogenate after cecal ligation and puncture, but not after LPS or fecal slurry injection. We investigated additional potential mechanistic explanations including differences in peritoneal bacterial clearance and host stool virulence. Our findings highlight the complex role of miR-223 in the pathogenesis of septic kidney injury, as well as the importance of differences in experimental sepsis models and their consequent translational applicability.

MiR-21-3p Plays a Crucial Role in Metabolism Alteration of Renal Tubular Epithelial Cells during Sepsis Associated Acute Kidney Injury via AKT/CDK2-FOXO1 Pathway

“…Factors involved in the pathophysiology of SAKI are multiple, while microRNA plays an important part [16,17]. MicroRNA is known to be one kind of noncoding RNAs that can regulate specific genes expression posttranscriptionally by targeting their mRNAs.…”

Analysis of Exosome-derived MicroRNAs as Early Biomarkers of Lipopolysaccharide-induced Acute Kidney Injury in Rats

“…The identi cation of urinary markers can be di cult because of the reduced urine output that is typical of most forms of AKI. In addition, several studies have identi ed miRNAs associated with sepsis-induced AKI [23][24][25][26][27][28][29]; however, most of these studies identi ed tissue miRNAs that would make them unlikely to be AKI biomarkers in clinical practice. miRNAs transported by microvesicles present in the serum are easily obtained with minimal invasiveness and can therefore be used as biomarkers of sepsis-induced AKI.…”

Perioperative Acute Kidney Injury

“…39,47 Similarly, a number of antiinflammatory pathways that can be targeted for acute kidney injury prevention or treatment have been identified, such as purinergic [48][49][50] or hypoxia-elicited antiinflammatory signaling pathways 51 or inflammatory endpoints that are under the control of microRNAs. 41,[52][53][54] Patient-associated Risk Factors for Acute Kidney injury Several elements are correlated with a heightened risk for perioperative acute kidney injury in patients. Preexisting perioperative elevation of creatinine (more than 1.2 mg/ dl) is a significant predictor for postoperative acute kidney injury among both cardiac and noncardiac surgery (GFr).…”