OBJECTIVE AND DESIGN Sepsis, a systemic inflammatory response syndrome, is still a common cause of death even the patients who are in the intensive care unit. Alleviating septic liver damage may be effective in improving sepsis. Necroptosis and miRNAs have been regarded as a potential target in sepsis. MATERIAL OR SUBJECTS The aim of this work is to explain the potential role of miR-425-5p in septic liver damage. LPS was intraperitoneal-injection to C57BL/6 mice for sepsis, and hepatocytes treated with septic serum in vitro. H&E staining for histological evaluation, luciferase reporter assay for target validation, and qRT-PCR, WB, and ELISA analysis for assessment of miR-425-5p, RIP1, inflammatory factors, and LDH levels. RESULTS Down-regulated miR-425-5p and up-regulated RIP1/RIP3 were in LPS-induced sepsis mice. Liver damage, RIP1-mediated necroptosis, IL-1β, and TNF-α were suppressed by miR-425-5p agomiR, but further aggravated by miR-425-5p antagomiR. Furthermore, we demonstrated miR-425-5p targeted the 3'UTR of RIP1 mRNA to inhibit RIP1 expression and activated RIP1 reversed miR-425-5p-induced suppression of necroptosis and inflammation in septic hepatocytes. CONCLUSIONS The data suggest miR-425-5p negatively controls the RIP1-mediated necroptotic signaling cascades and inflammation, and sepsis-related liver damage. miR-425-5p/RIP1 axis is a potential therapeutic strategy for sepsis-related liver damage through necroptosis and inflammation.

中文翻译：

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miR-425-5p通过负调控RIP1介导的坏死病改善炎症和败血性肝损害。

目的和设计脓毒症是一种全身性的炎症反应综合征，即使在重症监护病房的患者中，仍然是常见的死亡原因。减轻败血性肝损伤可能有效改善败血症。坏死病和miRNA被认为是脓毒症的潜在靶标。材料或受试者这项工作的目的是解释miR-425-5p在败血性肝损伤中的潜在作用。将LPS腹膜内注射至C57BL / 6小鼠以引起败血症，并在体外用化脓性血清处理肝细胞。H＆E染色用于组织学评估，荧光素酶报告基因分析用于靶标验证，qRT-PCR，WB和ELISA分析用于评估miR-425-5p，RIP1，炎性因子和LDH水平。结果在LPS诱导的败血症小鼠中，miR-425-5p的下调和RIP1 / RIP3的上调。肝损害，RIP1介导的坏死病，IL-1β和TNF-α被miR-425-5p agomiR抑制，但进一步被miR-425-5p antagomiR所加重。此外，我们证明了miR-425-5p靶向RIP1 mRNA的3'UTR来抑制RIP1表达并激活RIP1逆转了miR-425-5p诱导的化脓性肝细胞坏死病和炎症的抑制。结论数据提示miR-425-5p负控制RIP1介导的坏死性信号传导级联和炎症，以及败血症相关的肝损害。miR-425-5p / RIP1轴是通过坏死病和炎症而引起败血症相关性肝损害的潜在治疗策略。RIP1 mRNA的UTR抑制RIP1表达和激活的RIP1逆转了miR-425-5p诱导的败血性肝细胞坏死病和炎症的抑制。结论数据提示miR-425-5p负控制RIP1介导的坏死性信号传导级联和炎症，以及败血症相关的肝损害。miR-425-5p / RIP1轴是通过坏死病和炎症而引起败血症相关性肝损害的潜在治疗策略。RIP1 mRNA的UTR抑制RIP1表达和激活的RIP1逆转了miR-425-5p诱导的败血性肝细胞坏死病和炎症的抑制。结论数据提示miR-425-5p负控制RIP1介导的坏死性信号传导级联和炎症，以及败血症相关的肝损害。miR-425-5p / RIP1轴是通过坏死病和炎症而引起败血症相关性肝损害的潜在治疗策略。