The long non-coding RNA MALAT1 is increased in renal ischemia-reperfusion injury and inhibits hypoxia-induced inflammation

Hongyan Tian,Ming Wu,Peihui Zhou,Chuiguo Huang,Chaoyang Ye,Li Wang

doi:10.1080/0886022x.2018.1487863

Abstract

Background: To investigate the expression of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in renal ischemia-reperfusion injury and explore its role in acute kidney injury.Methods: 18 mice were randomly divided into a sham operation group (Sham) and an ischemia-reperfusion group (IR) in which animals were sacrificed at 6 h or 12 h after surgery. The kidneys were harvested to measure the expression of MALAT1 mRNA. HK2 cells were treated with cobalt chloride (CoCl2) to mimic hypoxia or transfected with siRNA to knockdown MALAT1 before CoCl2 treatment. After that, MALAT1 was analyzed by RT-PCR (reverse transcription-polymerase chain reaction). HIF-1ɑ (hypoxia-inducible factor-1 alpha) and NF-κB (nuclear factor-kappa B) was measured by Western blot. The concentrations of IL-6 (interleukin-6) and TNF-ɑ (tumor necrosis factor-alpha) in the media were detected by ELISA (enzyme-linked immunosorbent assay).Results: The expression of MALAT1 in the IR (6 h/12 h) group was significantly higher than that in the sham group. In HK2 cells, MALAT1 was significantly increased at 1 h, 3 h, and 6 h after CoCl2 treatment but had reduced to the basal level at 12 h and 24 h. Knockdown of MALAT1 by siRNA significantly up-regulated the expression of HIF-1ɑ and NF-κB proteins in CoCl2-treated HK2 cells. In addition, the concentrations of IL-6 and TNF-ɑ were increased by MALAT1 siRNA transfection in CoCl2-treated HK2 cells.Conclusion: The expression of MALAT1 is increased in renal ischemia-reperfusion injury. It is likely that MALAT1 inhibits the hypoxia-induced inflammatory response through the NF-κB pathway.

Highlights

Acute kidney injury (AKI) is a common complication in hospitalized patients, especially in the intensive care unit (ICU)
We demonstrated that (1) the expression of the Long non-coding RNAs (lncRNAs) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was up-regulated in a mouse model of AKI induced by ischemia/reperfusion and (2) knocking-down MALAT1 enhanced HK2 cell inflammation (IL-6/tumor necrosis factor alpha (TNF-a)) in chemically mimicked hypoxia
It remained unknown whether the expression of MALAT1 is increased in renal ischemia/reperfusion injury

Summary

Introduction

Acute kidney injury (AKI) is a common complication in hospitalized patients, especially in the intensive care unit (ICU). Ischemia-reperfusion injury (IRI) is one of the most common causes of acute kidney injury (AKI), which is associated with high rates of morbidity and mortality in clinics [9,10]. Inflammation is a complicated biological response that mediates tissue repair after injury, and it is involved in the pathology of IRI-induced AKI, as shown in many experimental studies [11]. Hypoxiainducible factor 1 (HIF-1a) is a central mediator of cellular adaptation to hypoxia and plays a pivotal role in the pathogenesis of AKI [13].Interestingly, the reciprocal regulation of HIF-1a and NF-jB has been shown, which further complicates our understanding of the underlining mechanism of AKI [14]. To investigate the expression of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in renal ischemia-reperfusion injury and explore its role in acute kidney injury. In HK2 cells, MALAT1 was significantly increased at 1 h, 3 h, and 6 h after

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