Abstract
There is no effective treatment for septic acute kidney injury (AKI), which is considered a major public health concern in today’s world. Here, we studied the functions of miR-191-5p in septic AKI. MiR-191-5p mimic or mimic control was injected into rats from caudal vein before cecal ligation and puncture (CLP) surgery. Part of kidney tissues was stained by Hematoxylin and Eosin (H&E) for histological examination. The levels of serum cytokines were evaluated using enzyme-linked immunosorbent assay (ELISA). For cell transfection, renal cells were isolated from the kidneys of CLP rat model injected with mimic control and miR-191-5p mimic. With TargetScan prediction, serine/threonine-protein kinase OSR1 was identified as a target of miR-191-5p. Oxidative stress responsive 1 (OXSR1) overexpression vector was transfected into renal cells. Cell viability and apoptosis rate were determined by Cell Counting Kit-8 (CCK-8) and flow cytometry, respectively. We additionally measured the phosphorylation levels of p38 and p65. We found that the injection of miR-191-5p mimic could observably inhibit renal injury scores, and inhibit inflammatory cytokine productions and apoptotic protein levels in septic rats. After being transfected with OXSR1, the apoptosis rates and expressions of B-cell lymphoma-2 (Bcl-2), down-regulated Bax and Cleaved caspase-3 (C caspase-3) indicated overexpressed OXSR1 contributed to cell apoptosis. The up-regulated protein levels of p-p38 and p-p65 may suggest the involvement of p38 MAPK/NF-κB signaling pathway in the functions of OXSR1. Our results showed that the protective effects of miR-191-5p on kidney tissues of septic rats may rely on the repression of OXSR1.
Highlights
Sepsis is a condition characterized by a systemic inflammatory response syndrome (SIRS) triggered by infections of bacteria, virus or fungus [1,2]
In order to confirm the functions of miR-191-5p in the progression sepsis-induced acute kidney injury (AKI), we observed the histopathological changes in the kidneys of septic rat models with or without the effects of miR-191-5p
We found that the cecal ligation and puncture (CLP) surgery could induce the down-regulation of B-cell lymphoma-2 (Bcl-2) and up-regulation of Bax and C caspase-3, but enhancing miR-191-3p levels could effectively inhibit the induction of surgery (P
Summary
Sepsis is a condition characterized by a systemic inflammatory response syndrome (SIRS) triggered by infections of bacteria, virus or fungus [1,2]. The host response to infections causes the failure of multiple organs, the kidney is one of the most commonly affected organs [3]. Septic acute kidney injury (AKI) is one of the most severe and frequent complications of sepsis [4]. Recent studies indicated that the pathogenesis of sepsis-induced AKI contains a series of complex interactions between the dysfunction of vascular endothelial cells, inflammatory response and tubular cell apoptosis [7–9], efforts to translate the findings from bench to bedside in clinical trials have been proven to be failed. A more complete understanding of the pathogenesis of septic kidney injury is required for developing more effective therapeutic strategies
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