Abstract
Purpose Ample evidence has proved that lncRNAs are pivotal regulators in acute kidney injury (AKI). Here, we focus on the role and mechanism of lncRNA SNHG14 in ischemia/reperfusion- (I/R-) caused AKI. Methods I/R and hypoxia/reoxygenation (H/R) were applied to induce rats and HK-2 cells to establish AKI models in vivo and in vitro. Relative expression of SNHG14, miR-124-3p, and MMP2 was determined by qRT-PCR. HE staining was used to evaluate pathological changes in renal tissues, and acute tubular necrosis (ATN) score was calculated. Renal function was evaluated by measuring serum creatinine content and blood urea nitrogen content. Levels of IL-1β, IL-6, and TNF-α were measured by ELISA. Cell viability was examined by MTT assay. Oxidative stress was assessed by measuring SOD, MDA, and ROS levels. The target of SNHG14 or miR-124-3p was verified by DLR assay. Protein expression of MMP2 was examined by western blot. Results SNHG14 was boosted in renal tissues of I/R-stimulated rats and H/R-induced HK-2 cells, while miR-124-3p was diminished in H/R-stimulated HK-2 cells. Si-SNHG14 or miR-124-3p mimics repressed inflammation and oxidative stress and enhanced cell viability in H/R-stimulated HK-2 cells. Sh-SNHG14 mitigated I/R-induced AKI in rats. MiR-124-3p was targeted by SNHG14, and MMP2 was targeted by miR-124-3p. Inhibition of miR-124-3p or upregulation of MMP2 reversed inhibitory effects of SNHG14 silence on inflammation and oxidative stress as well as the promoting effect of SNHG14 silence on cell viability in H/R-induced HK-2 cells. Conclusion Knockdown of SNHG14 alleviated I/R-induced AKI by miR-124-3p-mediated downregulation of MMP2.
Highlights
Acute kidney injury (AKI) is defined as a sudden decline of kidney function [1]
I/R treatment contributed to the increases of relative serum Cr content and relative BUN content, which was reversed by the addition of sh-small nucleolar RNA host gene 14 (SNHG14) in serum of I/R-induced rats (all P < 0:01, Figures 1(c) and 1(d))
AKI refers to is a common complication in hospitalized patients and renal I/R injury is implicated in the pathophysiology of AKI [41, 42]
Summary
Acute kidney injury (AKI) is defined as a sudden decline of kidney function [1]. Excessive production of inflammatory cytokines, necrosis, apoptosis, and delayed proliferation of renal resident cells are major pathological features of AKI [2,3,4]. As a common contributor of AKI [5], renal ischemia-reperfusion (I/R) injury leads to injury of different degrees to renal tissues, which is related to the increment of morbidity and mortality [6,7,8]. It arises from momentary interruption of blood supply followed by restoring blood supply, which fails to restore renal functions and causes structural damage [9, 10]. Exploring a new strategy to alleviate I/R-induced renal injury is urgent and imperative for developing effective treatments of AKI
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