1. Academic Validation
  2. 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

  • JCI Insight. 2021 Jan 25;6(2):e138584. doi: 10.1172/jci.insight.138584.
Juanjuan Dai 1 2 Mingjie Jiang 2 Yangyang Hu 1 2 3 Jingbo Xiao 1 2 Bin Hu 1 2 Jiyao Xu 4 Xiao Han 1 2 Shuangjun Shen 1 2 Bin Li 1 2 Zengkai Wu 1 2 Yan He 1 2 Yingchun Ren 1 2 Li Wen 1 2 Xingpeng Wang 1 2 Guoyong Hu 1 2
Affiliations

Affiliations

  • 1 Department of Gastroenterology and.
  • 2 Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • 3 Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
  • 4 Department of Emergency, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Abstract

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 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 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.

Keywords

Epigenetics; Gastroenterology; Insulin; Molecular pathology; Therapeutics.

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