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. 2022 Dec;37(12):2855-2864.
doi: 10.1002/tox.23642. Epub 2022 Sep 2.

Downregulation of circ-ZNF644 alleviates LPS-induced HK2 cell injury via miR-335-5p/HIPK1 axis

Junzuo Gong  1 , Shiqiao Zhao  1 , Shu Luo  1 , Songlin Yin  1 , Xiaofeng Li  1 , Yao Feng  1
Affiliations

Downregulation of circ-ZNF644 alleviates LPS-induced HK2 cell injury via miR-335-5p/HIPK1 axis

Junzuo Gong et al. Environ Toxicol. 2022 Dec.

Abstract

Circular RNA (circRNA) has been confirmed to be involved in regulating sepsis-induced acute kidney injury (AKI). Our research aims to explore circ-ZNF644 role in the development of sepsis-induced AKI. Lipopolysaccharide (LPS) was used to induce kidney tubular epithelial cell (HK2) injury. ELISA assay was performed to measure the concentrations of inflammation factors. Cell functions were determined by cell counting kit 8 assay, EdU assay and flow cytometry. Protein expression was evaluated by Western blot analysis. Quantitative real-time PCR was used to detect relative expression of circ-ZNF644, miR-335-5p and homeodomain-interacting protein kinase 1 (HIPK1). RNA interaction was confirmed by dual-luciferase reporter assay and RIP assay. LPS enhanced HK2 cell inflammation, oxidative stress, apoptosis, and reduced proliferation. Circ-ZNF644 was overexpressed in sepsis-induced AKI patients. Circ-ZNF644 knockdown suppressed LPS-induced HK2 cell injury, and this effect could be revoked by miR-335-5p inhibitor. MiR-335-5p was sponged by circ-ZNF644, and its expression was downregulated in sepsis-induced AKI patients. HIPK1 was targeted by miR-335-5p, and its expression could be suppressed by circ-ZNF644 knockdown. MiR-335-5p had an inhibition effect on HK2 cell injury induced by LPS, and HIPK1 overexpression could reverse this effect. Circ-ZNF644 knockdown relieved LPS-induced HK2 cell injury through the miR-335-5p/HIPK1 axis, confirming that circ-ZNF644 contributed to sepsis-induced AKI.

Keywords: AKI; HIPK1; circ-ZNF644; miR-335-5p; sepsis.

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References

REFERENCES

    1. Poston JT, Koyner JL. Sepsis associated acute kidney injury. BMJ. 2019;364:k4891.
    1. Keir I, Kellum JA. Acute kidney injury in severe sepsis: pathophysiology, diagnosis, and treatment recommendations. J Vet Emerg Crit Care (San Antonio). 2015;25:200-209.
    1. Buttner S, Stadler A, Mayer C, et al. Incidence, risk factors, and outcome of acute kidney injury in neurocritical care. J Intensive Care Med. 2020;35:338-346.
    1. Peerapornratana S, Manrique-Caballero CL, Gomez H, Kellum JA. Acute kidney injury from sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment. Kidney Int. 2019;96:1083-1099.
    1. Ju M, Liu B, He H, et al. MicroRNA-27a alleviates LPS-induced acute lung injury in mice via inhibiting inflammation and apoptosis through modulating TLR4/MyD88/NF-kappaB pathway. Cell Cycle. 2018;17:2001-2018.

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