miR-103a-3p Could Attenuate Sepsis-Induced Liver Injury by Targeting HMGB1
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ORIGINAL ARTICLE
miR-103a-3p Could Attenuate Sepsis-Induced Liver Injury by Targeting HMGB1 Leifeng Chen,1 Qiang Lu,2 Fumou Deng,2 Shengliang Peng,2 Jiajia Yuan,2 Chunfang Liu,2 and Xiaohong Du 2,3
Abstract— The liver is one of the most vulnerable organs during sepsis. Current studies have
proven that microRNAs play important roles in injury and inflammation. The current study aimed to investigate the role of miR-103 in septic liver injury. The sepsis model was established by cecal ligation and puncture in mice. Then, the mice were divided into four groups: normal group, sepsis group, sepsis + miR-103a-3p agomir group, and sepsis + negative control group. Liver injury was observed by hematoxylin-eosin staining and electron microscopic studies. The sepsis-induced apoptosis in liver tissues was assessed by TUNEL staining. The levels of inflammatory cytokines in liver tissues were determined by enzymelinked immunosorbent assay kits. The targeted gene of miR-103a-3p in cells was predicted by bioinformatics algorithm and confirmed by dual-luciferase reporter assay. The expression of miR-103a-3p, HMBG1, and the apoptosis-relative proteins was examined by quantitative real-time polymerase chain reaction and Western blotting. miR-103a-3p was downregulated in liver tissues of sepsis animals. miR-103a-3p agomir could alleviate liver injury including the tissue injury and mitochondrial damage, inhibit the secretion of inflammatory factors, and decrease the apoptosis of liver cells. The high-mobility group B1 (HMGB1) was overregulated in sepsis, and it was a downstream target gene of miR-103a-3p. The results of the rescue assay confirmed that miR-103a-3p had a protection role in septic liver injury by targeting HMGB1. In summary, HMGB1 was one of the genes targeted by miR-103a-3p, which played roles in septic injury. These data may provide novel insight for the identification of new target and treatment strategies for septic liver injury. KEY WORDS: miR-103a-3p; HMGB1; Liver injury; Inflammation; Sepsis.
Qiang Lu contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10753-020-01275-0) contains supplementary material, which is available to authorized users. 1
Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, China 2 Department of Anesthesiology, Second Affiliated Hospital of Nanchang University, Nanchang, China 3 To whom correspondence should be addressed at Department of Anesthesiology, Second Affiliated Hospital of Nanchang University, Nanchang, China. E-mail: [email protected]
0360-3997/20/0000-0001/0 # 2020 Springer Science+Business Media, LLC, part of Springer Nature
Chen, Lu, Deng, Peng, Yuan, Liu, and Du INTRODUCTION
MATERIALS AND METHODS
Sepsis was the leading cause of mortality in the intensive care unit, which kills more than 750,000 patients annually. Severe sepsis is characterized by overwhelming inflammatory responses that cause multiple organ failure [1–3]. As an important organ in ho
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