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Dexmedetomidine Suppressed the Biological Behavior of HK-2 Cells Treated with LPS by Down-Regulating ALKBH5

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Abstract

Dexmedetomidine inhibits the release of inflammatory cytokines and exerts a systemic anti-inflammatory effect and has potential protective effects on vital organs such as lung, heart, and kidneys. The aim of this study was to investigate the effect of dexmedetomidine on LPS-treated HK-2 cells in vitro and explore the potential mechanisms. The HK-2 cells were pretreated with dexmedetomidine before LPS induction. CCK-8, flow cytometry, ELISA, or qRT-PCR was performed to detect cell proliferation, apoptosis, and proinflammatory cytokine expression. The levels of MALAT1 in HK-2 cells under different stimulation were measured by qRT-PCR. Then, m6A RNA immunoprecipitation was performed to detect methylated MALAT1 in HK-2 cells. The results showed dexmedetomidine suppressed cell viability, induced cell apoptosis, and reduced inflammation cytokine production of LPS-treated HK-2 cells. Besides, dexmedetomidine reduced the expression of MALAT1 in HK-2 cells under LPS stimulation. In addition, ALKBH5 could up-regulate MALAT1 expression by demethylation. Furthermore, dexmedetomidine inhibited the expression of ALKBH5 in LPS-treated HK-2 cells. ALKBH5 knockdown inhibited cell viability, induced cell apoptosis, and decreased inflammation cytokine production of LPS-treated HK-2 cells. In short, dexmedetomidine suppressed the biological behavior of HK-2 cells treated with LPS by inhibiting the expression of ALKBH5 in vitro, which may provide potential targets for the prevention and treatment of sepsis-induced kidney injury.

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  1. Department of Anesthesiology, Eastern Hospital, Sichuan Academy of Medical Science & Sichuan Province People’s Hospital, No.585, Honghe North Road, Damian Town, Longquanyi District, Chengdu, 610072, China

    Shaomin Zhu & Yu Lu

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The study was approved by the Medical Ethics Committee of Sichuan Academy of Medical Science, Sichuan Province People’s Hospital.

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Zhu, S., Lu, Y. Dexmedetomidine Suppressed the Biological Behavior of HK-2 Cells Treated with LPS by Down-Regulating ALKBH5. Inflammation 43, 2256–2263 (2020). https://doi.org/10.1007/s10753-020-01293-y

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