LncRNA MIAT Promotes Inflammation and Oxidative Stress in Sepsis-Induced Cardiac Injury by Targeting miR-330-5p/TRAF6/NF
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LncRNA MIAT Promotes Inflammation and Oxidative Stress in Sepsis‑Induced Cardiac Injury by Targeting miR‑330‑5p/ TRAF6/NF‑κB Axis Peng‑Cheng Xing, et al. [full author details at the end of the article] Received: 23 December 2019 / Accepted: 30 May 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Sepsis is a whole-body inflammation and main cause of death in intensive care units worldwide. We aimed to investigate the roles of lncRNA MIAT and miR-330-5p in modulating inflammatory responses and oxidative stress in lipopolysachariden (LPS)-induced septic cardiomyopathy. Serum and heart tissue were collected from in vivo septic mice model, ELISA and qRT-PCR were used to measure the expression of pro-inflammation cytokines, MIAT and miR-330-5p, respectively. The knockdown of MIAT and overexpression of miR-330-5p were conducted to assess their effects on regulating inflammation response and intracellular oxidative stress in LPS-stimulated HL-1 cells. The reactive oxygen (ROS) level, mitochondrial membrane potential (MMP), GSH/GSSH ratio, and lipid peroxidation assessment (MDA) were used to evaluate the intracellular oxidative stress. Dual-luciferase reporter assay was performed to identify the association between MIAT and miR-330-5p, TRAF6 and miR-330-5p, respectively. In septic mice, the expression of MIAT and pro-inflammation cytokines was elevated while the expression of miR-330-5p decreased. Knockdown of MIAT or overexpression of miR-330-5p restrained inflammation and oxidative stress induced by LPS in vitro; MIAT directly targeted miR-330-5p to regulate NF-κB signaling, and miR-330-5p targeted against TRAF6 to suppress the activation of NF-κB signaling. We determined that lncRNA MIAT directly binds to miR-330-5p to activate TRAF6/NF-κB signaling axis and further promotes inflammation response as well as oxidative stress in LPS-induced septic cardiomyopathy. This finding suggests the potential therapeutic role of lncRNA MIAT and miR-330-5p in LPS-induced myocardial injury. Keywords MIAT · miR-330-5p · TRAF6 · NF-κB · LPS-induced sepsis · Cardiomyopathy
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s1052 8-020-09976-9) contains supplementary material, which is available to authorized users.
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Biochemical Genetics
Background Sepsis is a systematic inflammation disease triggered by pathogens after infection, severe trauma, major surgeries and usually accompanied with multiple organ failure (Wu 2016). It is one of the leading causes of death in intensive care units globally (Zou 2014). Evidence demonstrated that myocardial dysfunction is a fatal complication that develops in patients with septic shock or sever sepsis (Tsolaki 2017). Sepsis-induced cardiomyopathy could be observed in over 50% of septic patients, which suggests a worse prognosis (Rudiger and Singer 2007). The increased reactive oxygen (ROS) and nitrogen species (RNS) production from cardiac mitochondria are highly associated with myocardial inj
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