Dexmedetomidine Suppressed the Biological Behavior of HK-2 Cells Treated with LPS by Down-Regulating ALKBH5
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ORIGINAL ARTICLE
Dexmedetomidine Suppressed the Biological Behavior of HK-2 Cells Treated with LPS by Down-Regulating ALKBH5 Shaomin Zhu1 and Yu Lu
1,2
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 LPStreated 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. Abstract—
KEY WORDS: dexmedetomidine; HK-2 cells; ALKBH5; MALAT1.
INTRODUCTION 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 2 To whom correspondence should be addressed at 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. E-mail: [email protected]
Sepsis is a systemic inflammatory syndrome with acute onset, rapid development and high mortality. It is often complicated by various stress conditions such as severe trauma, burns, infection, and major surgery, which can induce multi-organ dysfunction and has become one of the main causes of death in critical patients [4, 23]. The kidney is one of the most vulnerable organs to sepsis, and acute kidney injury (AKI) occurs in approximately 42% of
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Zhu, and Lu sepsis patients [3]. Studies have shown that sepsis is the major cause of about 50% of patients with severe AKI, and despite the use of antibiotics or immunoregulatory therapy, multiple organ function impairment are still not effectively controlled [1
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