Dysregulated SREBP1c/miR-153 signaling induced by hypertriglyceridemia worsens acute pancreatitis and delays tissue repair
| العنوان: | Dysregulated SREBP1c/miR-153 signaling induced by hypertriglyceridemia worsens acute pancreatitis and delays tissue repair |
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| المؤلفون: | Juanjuan Dai, Yangyang Hu, Guoyong Hu, Bin Hu, Yan He, Ming-jie Jiang, Jingbo Xiao, Zengkai Wu, Ying-Chun Ren, Shuangjun Shen, Jiyao Xu, Li Wen, Xingpeng Wang, Xiao Han, Bin Li |
| المصدر: | JCI Insight, Vol 6, Iss 2 (2021) JCI Insight |
| بيانات النشر: | American Society for Clinical investigation, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, medicine.medical_treatment, Therapeutics, Rats, Sprague-Dawley, Mice, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, medicine, Insulin, Animals, Humans, Regeneration, Pancreas, Transcription factor, Molecular pathology, Hypertriglyceridemia, Lipoprotein lipase, TNF Receptor-Associated Factor 3, business.industry, Regeneration (biology), Gastroenterology, General Medicine, medicine.disease, Rats, Up-Regulation, Mice, Inbred C57BL, Disease Models, Animal, Lipoprotein Lipase, MicroRNAs, 030104 developmental biology, medicine.anatomical_structure, Pancreatitis, 030220 oncology & carcinogenesis, Cancer research, Acute pancreatitis, Medicine, Epigenetics, Sterol Regulatory Element Binding Protein 1, business, Research Article, Signal Transduction |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 2379-3708 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1ef8f91905b98b576ba6a1badc696a31Test https://doaj.org/article/237cdc181b8943d08c3eb74f80888ecdTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1ef8f91905b98b576ba6a1badc696a31 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23793708 |
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