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Upregulation of miR-142-5p induced by lipopolysaccharide contributes to apoptosis of hepatocytes and hepatic failure

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机构: [1]Third Ward of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province, China [2]Department of Hepatopancreatobiliary Surgery, The First People’s Hospital of Yunnan Province, Kunming City, Yunnan Province, China [3]The Affiliated Hospital of Kunming University of Science and Technology, Kunming City, Yunnan Province, China [4]Second Ward of Hepatobiliary and Pancreatic Surgery, Second Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province, China [5]Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming city, Yunnan, China [6]Department of 1 Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province, China
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关键词: MiR-142-5p Septic liver injury Hepatocytes Hepatic failure

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OBJECTIVE: This study was probed to uncover the mechanism of miR-142-5p in septic liver injury. MATERIALS AND METHODS: In this study, in-vitro and in-vivo models of sepsis were used. For In-vitro sepsis model, hepatocyte cell line (L02 cells) was treated with LPS (I i popolysaccharide). Whereas for in-vivo sepsis model, cecal ligation and puncture were performed in mice. Mice were assigned into three groups: control, CLP (Cecal Ligation Puncture), CLP + miR-142-5p inhibitor group. Liver injury was assessed via H&E staining. IL-6, TNF-alpha, and IL-1 beta expressions were assayed through ELISA kits. C-caspase-9, C-caspase-3, ERK, p65, and I kappa B alpha expressions were determined via western blot and RT-qPCR. Apoptosis in LPS-induced L02 cells was detected by TUNEL staining. RESULTS: Our results show that miR-142-5p exhibited perspicuous upregulation in CLP mice tissues and LPS-induced L02 cells. On the other hand, inhibition of miR-142-5p could promote LPS-induced L02 cell activity and reduce apoptosis and inflammation. In terms of molecular mechanism, downregulation of miR-142-5p could abate sepsis-mediated acute hepatic injury by targeting SOCS1, through ERK and NF-kappa B pathway. CONCLUSIONS: Overall our results demonstrate that miR-142-5p inhibitors can mitigate septic liver injury by downregulating the inflammation and apoptosis via targeting SOCS1. Thus, miR-142-5p can serve a potential therapeutic target for sepsis mediated acute hepatic injury.

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出版当年[2022]版:
大类 | 4 区 医学
小类 | 4 区 药学
最新[2023]版:
大类 | 4 区 医学
小类 | 4 区 药学
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Q2 PHARMACOLOGY & PHARMACY
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第一作者机构: [1]Third Ward of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province, China
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