MiR-494-mediated Effects on the NF-κB Signaling Pathway Regulate Lipopolysaccharide-Induced Acute Kidney Injury in Mice

ABSTRACT

Objective

To explore the effects of miR-494 inhibition through the NF-κB signaling pathway on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) mouse model.

Methods

The AKI mice induced by LPS were treated with miR-494 antagomir, and the kidney parameters and indicators of oxidative stress were detected. HE and TUNEL staining were performed to observe the kidney histopathology and the apoptosis in renal tubular epithelial cells (RTECs), respectively. The ROS level was measured using dihydroethidium (DHE) staining. In addition, qRT-PCR, western blotting, immunohistochemistry (IHC), and ELISA were also used to detect gene or protein expression.

Results

LPS-induced AKI mice injected with the miR-494 antagomir showed reduced blood urea nitrogen (BUN) and serum creatinine (Cr) with improved kidney histopathology. The expression levels of p-IKKα/β, p-IκBα and p65 NF-κB in the nucleus were increased in kidney tissues from the LPS-induced AKI mice, and they were decreased by the miR-494 antagomir. Moreover, the results of IHC showed that the miR-494 antagomir downregulated p65 NF-κB in kidney tissues from the LPS-induced AKI mice, accompanied by decreased levels of TNF-α, IL-1β, IL-6, MDA, NO, and ROS but increased levels of SOD and GSH. In addition, the LPS-induced AKI mice had increased apoptosis in RTECs, as well as increased Caspase-3 and Bax and decreased Bcl-2, which were reversed by the miR-494 antagomir.

Conclusions

The inhibition of miR-494 could reduce inflammatory responses and improve oxidative stress in kidney tissues from LPS-induced AKI mice by blocking the NF-κB pathway accompanying by reduced apoptosis in RTECs.

KEYWORDS:

• Acute kidney injury
• lipopolysaccharide
• miR-494
• NF-κB signaling pathway

Acknowledgments

The study was supported by Cangzhou Science and Technology R&D Instruction Project (No. 183302086).

Authors’ contributions

Peng Lu and Lei Zhang designed the study, Ting Liu and Jing–Jing Fan performed and analyzed the experiments, Xu Luo and Yi-Tang Zhu drafted and revised the manuscript.

Declarations of interest

The authors report no declarations of interest.