MTMR14 protects against hepatic ischemia-reperfusion injury through interacting with AKT signaling in vivo and in vitro - 28/08/20
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Highlights |
• | MTMR14 inhibits ischemia reperfusion (IR) injury-triggered hepatic dysfunction and cell death. |
• | MTMR14 suppresses IR-triggered hepatic inflammation. |
• | MTMR14 interacts with AKT to meditate cell death and inflammation during hepatic IR injury. |
Abstract |
Hepatic ischemia-reperfusion (IR) injury is characterized by severe inflammation and cell death. However, very few effective therapies are presently available for hepatic IR injury treatment. Here, we reported a protective function and the underlying mechanism of myotubularin-related protein 14 (MTMR14) during hepatic IR injury. Hepatocyte-specific MTMR14 knockout (HKO) and transgenic (TG) mice were subjected to hepatic IR operation to explore MTMR14 function in vivo. Primary hepatocytes isolated from MTMR14-HKO and MTMR14-TG mice were subjected to hypoxia/reoxygenation (HR) insult in vitro. We found that MTMR14 expression in liver tissues from individuals with hepatic IR was markedly decreased, and similar results were detected in mice with hepatic IR surgery. MTMR14-TG mice following hepatic IR operation had obviously ameliorated liver pathological changes, along with improved hepatic dysfunction, which was proved by the decreased serum alanine amino transferase (ALT) and aspartate amino transferase (AST) levels. MTMR14-HKO and MTMR14-TG animal models indicated that MTMR14 alleviated cell death and inflammatory response. In addition, MTMR14 inhibited nuclear transcription factor κB (NF-κB) signaling. Of note, promoting MTMR14 expression improved phosphatidylinositol 3-kinase/protein kinase-B (PI3K/AKT) pathway through a physical interaction with AKT, subsequently reducing cell death and inflammation. Therefore, MTMR14 is a protective factor during hepatic IR injury, and the MTMR14/AKT signaling is involved the pathogenesis hepatic IR injury. Improvement of this axis might be a novel therapeutic strategy for the prevention of this pathological process.
El texto completo de este artículo está disponible en PDF.Keywords : Hepatic IR injury, MTMR14, Cell death, Inflammation, AKT
Esquema
Vol 129
Artículo 110455- septembre 2020 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.
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