Abstract
The present study was designed to investigate the involvement of miR-23a-3p in the progression of sepsis-induced acute kidney injury (AKI). The expression levels of miR-23a-3p and wnt5a in sepsis-induced AKI patients and lipopolysaccharide (LPS)-treated HK-2 cells were detected by real-time PCR and western blotting. Then, the effects of miR-23a-3p overexpression on cell viability, apoptosis, and inflammatory cytokines secretion in LPS-stimulated HK-2 cells were investigated. Moreover, luciferase reporter assay was performed to confirm the regulatory relationship between miR-23a-3p and wnt5a. Whether miR-23a-3p regulated the activation of Wnt/β-catenin signaling was also explored. mR-23a-3p was lowly expressed in the serum of patients with sepsis-associated AKI and in LPS-treated HK-2 cells. In addition, the overexpression of miR-23a-3p restrained LPS-induced proliferation inhibition and promotion of apoptosis and cytokine production in HK-2 cells. Moreover, wnt5a was identified as a target of miR-23a-3p, which could be negatively regulated by miR-23a-3p. Overexpression of miR-23a-3p suppressed the activation of Wnt/β-catenin signaling in LPS-treated HK-2 cells, which was markedly reversed by wnt5a upregulation. Upregulation of miR-23a-3p may alleviate LPS-induced cell injury by targeting wnt5a and inactivating Wnt/β-catenin pathway, which may serve as a novel therapeutic target for sepsis-associated AKI.
Highlights
Sepsis is a systemic inflammatory condition caused by the invasion of pathogens, leading to fatal multiple organ dysfunction syndrome (MODS) [1,2]
The results demonstrated that miR23a-3p expression was significantly decreased in serum of patients with sepsis-induced acute kidney injury (AKI) compared to healthy controls (Figure 1A). miR-23a-3p expression was suppressed in LPS-treated HK-2 cells compared to the untreated cells (Figure 1B)
The results of CCK-8 cell viability assay showed that compared to the untreated HK-2 cells, LPS treatment reduced the cell viability, while the overexpression of miR-23a-3p markedly increased the viability of LPS-stimulated HK-2 cells (Figure 2B)
Summary
Sepsis is a systemic inflammatory condition caused by the invasion of pathogens, leading to fatal multiple organ dysfunction syndrome (MODS) [1,2]. 50% of patients with sepsis will develop acute kidney injury (AKI) that is characterized by the rapid decline and even loss of kidney function [3]. AKI is a life-threatening complication of sepsis, which is implicated in increased morbidity and mortality in the intensive care unit [4,5]. Many urinary and serum biomarkers have been described as increased in kidney injury, such as cystatin C, kidney injury molecule-1, among others, but they are not effective in reflecting kidney damage [6]. Research has proposed that the release of inflammatory mediators, kidney hemodynamic abnormality, as well as microcirculation dysfunction and kidney cell apoptosis caused by kidney injury are involved in the pathogenesis of sepsis-associated AKI [7,8]. It is critical to identify potential biomarkers for early diagnosis, treatment, and prognosis of septic AKI
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