Linc-KIAA1737\u20132 promoted LPS-induced HK-2 cell apoptosis by regulating miR-27a-3p/TLR4/NF-\u03baB axis

Ming Hu,Jianhua Xu,Jing Wei,Shijun Lu,Haiyuan Li,Chao Ning,Liu Yang,Zhaofeng He

doi:10.1007/s10863-021-09897-1

Abstract

Inflammation and renal cell apoptosis participate in sepsis-induced acute kidney injury. Previous research found the upregulation of long non-coding RNA Linc-KIAA1737–2 in hypoxia- or inflammation-challenged human proximal tubular epithelial cells, but its role in sepsis-induced acute kidney injury is underexplored. In this research, we found that Linc-KIAA1737–2 could be upregulated in HK-2 human proximal tubular epithelial cells by LPS treatment, and knock-down of this lncRNA significantly attenuated LPS-induced apoptosis in HK-2 cells, while its overexpression showed opposite effect. MiR-27a-3p was confirmed to interact with Linc-KIAA1737–2 in HK-2 cells by RNA pull-down and dual-luciferase assay. MiR-27a-3p mimic transfection significantly attenuated LPS-induced HK-2 cell apoptosis by downregulating the protein levels of TLR4 and NF-κB, which was overturned by overexpression of Linc-KIAA1737–2. Our results suggested that Linc-KIAA1737–2 could promote LPS-induced apoptosis in HK-2 cells, and presumably sepsis-induced acute kidney injury, by regulating the miR-27a-3p/TLR4/NF-κB axis.

Highlights

LncRNA Linc-KIAA1737–2 has been found upregulated in hypoxia or pro-inflammatory cytokine-challenged proximal tubular epithelial cells (Lin et al 2015)
We found that Linc-KIAA1737–2 knock-down significantly reduced the protein levels of Tool-like receptor 4 (TLR4) and NF-κB in LPS induced-HK-2 cells, while the overexpression of this long non-coding RNAs (lncRNAs) showed opposite effects, as suggested by our western blotting assay results shown in Fig. 2D and 3D
We identified that Linc-KIAA1737–2 could be upregulated in HK-2 human proximal tubular epithelial cells by LPS treatment; knock-down of this lncRNA significantly attenuated LPSinduced apoptosis in HK-2 cells, while its overexpression showed opposite effect, suggesting the participation of this lncRNA in sepsis-induced acute kidney injury

Summary

Introduction

Sepsis is a life-threatening symptom that can lead to dysfunction of lung, liver and kidney. Sepsis is often characterized as systemic inflammatory response syndrome (Hotchkiss et al 2016). Epithelial cell apoptosis caused by inflammation and/or hypoxia is one of the major steps during the development of sepsis-induced. It is known that long non-coding RNAs (lncRNAs) can regulate gene expression by interacting with microRNAs (miRNAs). While miRNAs regulate gene expression by interacting with mRNAs, preventing mRNA translation and mediating their degradation through the RNA-induced silencing complex; lncRNAs, on the other hand, competitively bind to miRNAs, inhibiting their functions (Beermann et al 2016; Thomson and Dinger 2016).

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