A Model Specific Role of MicroRNA-223 as a Mediator of Kidney Injury During Experimental Sepsis.

A Model Specific Role of MicroRNA-223 as a Mediator of Kidney Injury During Experimental Sepsis. Am J Physiol Renal Physiol. 2017 May 17;:ajprenal.00493.2016 Authors: Colbert JF, Ford JA, Haeger SM, Yang Y, Dailey KL, Allison KC, Neudecker V, Evans CM, Richardson VL, Brodsky K, Faubel S, Eltzschig HK, Schmidt EP, Ginde AA 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 ...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research