Dysregulated SREBP1c/miR-153 signaling induced by hypertriglyceridemia worsens acute pancreatitis and delays tissue repair

Dysregulated SREBP1c/miR-153 signaling induced by hypertriglyceridemia worsens acute pancreatitis and delays tissue repair

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Severe acute pancreatitis (AP) is a life-threatening disease with up to 30% mortality.Therefore, prevention of AP aggravation and promotion of pancreatic regeneration are critical during the course and treatment of AP.Hypertriglyceridemia (HTG) is an established aggravating factor for AP that hinders pancreatic regeneration; however, its exact mechanism remains unclear.

Using miRNA sequencing and further verification, we found that miRNA-153 (miR-153) was upregulated in the pancreas of HTG animal models and in the plasma of patients with HTG-AP.Increased miR-153 aggravated HTG-AP and delayed sten jacket m pancreatic repair via targeting TRAF3.Furthermore, miR-153 was transcriptionally usc trojans snapback hat suppressed by sterol regulatory element-binding transcription factor 1c (SREBP1c), which was suppressed by lipoprotein lipase malfunction-induced HTG.

Overexpressing SREBP1c suppressed miR-153 expression, alleviated the severity of AP, and facilitated tissue regeneration in vivo.Finally, therapeutic administration of insulin also protected against HTG-AP via upregulating SREBP1c.Collectively, our results not only provide evidence that HTG leads to the development of more severe AP and hinders pancreatic regeneration via inducing persistent dysregulation of SREBP1c/miR-153 signaling, but also demonstrate that SREBP1c activators, including insulin, might be used to treat HTG-AP in patients.