Abstract
BackgroundStudies have shown that ginsenoside R3 (Rg3) plays a protective role in sepsis-induced organ injuries and mitochondrial dysfunction. Long noncoding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) is regarded as a regulator in sepsis. However, the association between TUG1 and Rg3 remains elusive.MethodsA sepsis mouse model was established by caecal ligation and puncture (CLP), and liver injury was induced by haematoxylin-eosin (H&E) staining. Lipopolysaccharide (LPS) was used to induce hepatocyte damage. The expression levels of TUG1, microRNA (miR)-200a-3p, and silencing information regulator 1 (SIRT1) were examined by quantitative real-time polymerase chain reaction (qRT–PCR) assays. Cell viability was monitored using the Cell Counting Kit-8 (CCK-8) assay. MitoSOX Red staining and CBIC2 (JC-1) dye were employed to detect mitochondrial reactive oxygen species (ROS) and mitochondrial transmembrane potential (MTP) levels, respectively. The interaction between miR-200a-3p and TUG1 or SIRT1 was confirmed via dual-luciferase reporter or RNA immunoprecipitation (RIP) assay.ResultsRg3 upregulated TUG1 expression in liver tissues of CLP mice and LPS-induced hepatocytes. Rg3 could activate autophagy to improve mitochondrial dysfunction in LPS-treated hepatocytes, which was partially reversed by TUG1 depletion or miR-200a-3p overexpression. Importantly, TUG1 targeted miR-200a-3p to activate the SIRT1/AMP-activated protein kinase (AMPK) pathway in LPS-treated hepatocytes. Moreover, gain of TUG1 ameliorated mitochondrial dysfunction in LPS-treated hepatocytes by sequestering miR-200a-3p.ConclusionOur study revealed that Rg3 increased TUG1 expression and reduced miR-200a-3p expression to stimulate the SIRT1/AMPK pathway, thereby enhancing autophagy to improve sepsis-induced liver injury and mitochondrial dysfunction.
Highlights
Studies have shown that ginsenoside R3 (Rg3) plays a protective role in sepsis-induced organ injuries and mitochondrial dysfunction
LncRNA taurine-upregulated gene 1 (TUG1) was involved in sepsis-induced liver injury and mitochondrial dysfunction improvement triggered by Ginsenoside R3 (Rg3) LncRNA TUG1 was proven to be associated with the development of sepsis [25]
We investigated the impact of Rg3 on LPS-induced human primary hepatocytes
Summary
Studies have shown that ginsenoside R3 (Rg3) plays a protective role in sepsis-induced organ injuries and mitochondrial dysfunction. Long noncoding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) is regarded as a regulator in sepsis. As the major contributor of death for patients admitted to the intensive care unit (ICU), sepsis generally induces dysfunction of multiple organs through diverse mechanistic pathways [3, 4]. The pathophysiology of sepsis is extremely complex, making current treatment less effective [5]. The liver can act as a lymphoid organ that mediates the immune response, removing bacteria and toxins, as well as inflammation, immune suppression, and organ injuries [6]. Reducing liver injury and restoring liver function are regarded as important strategies that can decrease the morbidity and mortality of patients with sepsis. It is necessary to explore in detail the molecular mechanism of sepsis progression to develop novel therapeutic targets and drugs
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