Yonsei Med J.  2021 May;62(5):461-469. 10.3349/ymj.2021.62.5.461.

MIR210HG Aggravates Sepsis-Induced Inflammatory Response of Proximal Tubular Epithelial Cell via the NF-κB Signaling Pathway

• Deng S
• Gu B
• Yu Z
• Shen Z
• Ren H

• KMID: 2515251
• DOI: http://doi.org/10.3349/ymj.2021.62.5.461

Abstract

Purpose
Acute kidney injury (AKI) is a serious complication of sepsis and is characterized by inflammatory response. MicroRNA-210 host gene (MIR210HG) is upregulated in human proximal tubular epithelial cells under treatment of inflammatory cytokines. This study aimed to explore the role of MIR210HG in sepsis-induced AKI.
Materials and Methods
Cell viability was detected by a cell counting kit 8 assay. The levels of proinflammatory cytokines were detected by enzyme-linked immunosorbent assay kits. The protein levels of p65, IκBα, and p-IκBα were examined by western blot analysis. The nuclear translocation of nuclear factor kappa B (NF-κB) was detected by immunofluorescence assay. The histological changes of kidneys were analyzed by hematoxylin and eosin staining assay.
Results
Lipopolysaccharide (LPS) treatment significantly inhibited cell viability and increased productions of proinflammatory cytokines in proximal tubular epithelial cells (HKC-8). Additionally, MIR210HG levels in HKC-8 cells were increased by LPS treatment. MIR210HG silencing inhibited the LPS-induced cell inflammatory response. MIR210HG activated the NF-κB signaling pathway by promoting the phosphorylation of IκBα and nuclear translocation of p65. Rescue assays revealed that the MIR210HGinduced increase of cytokines levels and decline of cell viability were rescued by QNZ treatment. Knockdown of MIR210HG decreased blood urea nitrogen, serum creatinine, and proinflammatory cytokine levels in AKI rats. Moreover, the knockdown of MIR210HG protected against AKI-induced histological changes of kidneys in rats.
Conclusion
MIR210HG promotes sepsis-induced inflammatory response of HKC-8 cells by activating the NF-κB signaling pathway. This novel discovery may be helpful for the improvement of sepsis-induced AKI.

Keyword

MIR210HG; sepsis; AKI; NF-κB signaling