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

Blog Article

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 Square Counter TBL Set (5/CN) 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 pancreatic repair via targeting TRAF3.Furthermore, miR-153 was transcriptionally 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 2 Seater Sofa 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.