Abstract
BackgroundSepsis is life-threatening disease with systemic inflammation and can lead to various diseases, including septic acute kidney injury (AKI). Recently, diverse circular RNAs (circRNAs) are considered to be involved in the development of this disease. In this study, we aimed to elucidate the role of circ-FANCA and the potential action mechanism in sepsis-induced AKI.MethodsHK2 cells were treated with lipopolysaccharide (LPS) to establish septic AKI cell model. The expression of circ-FANCA, microRNA-93-5p (miR-93-5p) and oxidative stress responsive 1 (OXSR1) mRNA was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was assessed using cell counting kit-8 (CCK-8) assay. Cell apoptosis and cell cycle distribution were measured by flow cytometry. The inflammatory response was monitored according to the release of pro-inflammatory cytokines via enzyme-linked immunosorbent assay (ELISA). The activities of oxidative indicators were examined using the corresponding kits. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were applied to validate the interaction between miR-93-5p and circ-FANCA or OXSR1. Protein analysis was conducted through western blot.ResultsCirc-FANCA was upregulated in septic AKI serum specimens and LPS-treated HK2 cells. Functionally, circ-FANCA knockdown facilitated cell proliferation and restrained apoptosis, inflammation and oxidative stress in LPS-triggered HK2 cells. Further mechanism analysis revealed that miR-93-5p was a target of circ-FANCA and circ-FANCA modulated LPS-induced cell damage by targeting miR-93-5p. Meanwhile, miR-93-5p overexpression repressed LPS-treated HK2 cell injury by sponging OXSR1. Furthermore, circ-FANCA regulated OXSR1 expression by sponging miR-93-5p. Besides, exosome-derived circ-FANCA was upregulated in LPS-induced HK2 cells, which was downregulated by GW4869.ConclusionCirc-FANCA knockdown attenuated LPS-induced HK2 cell injury by regulating OXSR1 expression via targeting miR-93-5p.
Highlights
Sepsis is life-threatening disease with systemic inflammation and can lead to various diseases, including septic acute kidney injury (AKI)
For the establishment of sepsis-related AKI model in vitro, HK2 cells in the following experiments were exposed to 5 μg/mL LPS (Solarbio, Beijing, China) for 12 h, while the control HK2 cells were cultivated with MEM medium simultaneously
Circ-FANCA knockdown dramatically elevated miR-93-5p expression, while circ-FANCA overexpression apparently decreased miR93-5p expression in LPS-treated HK2 cells (Fig. 3i). These results demonstrated that circ-FANCA negatively modulated miR-93-5p expression by directly targeting
Summary
Sepsis is life-threatening disease with systemic inflammation and can lead to various diseases, including septic acute kidney injury (AKI). Sepsis is a complicated systemic disease with high morbidity and fatality rate, which is caused by infection and can evoke organ dysfunction [1, 2]. Acute kidney injury (AKI) is a frequent sepsis-related complication with high incidence accompanied by acute. Previous study has suggested that natural killer T (NKT) cells were involved in the infectious and autoimmune diseases [4]. The accumulation of multifarious immune cells including NKT cells, CD4+ T cells, B cells and IFNγ-producing neutrophils are closely associated with the pathogenesis of AKI [8,9,10]. Lipopolysaccharide (LPS)-induced sepsis is a primary cause of AKI in critically ill patients [11, 12]. For the intricate pathogenesis of sepsis-induced AKI, exploring the latent mechanisms and effective therapeutic strategies are of great significance for AKI treatment
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