کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8726621 | 1590028 | 2018 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
HIF1-alpha Regulates Acinar Cell Function and Response to Injury in Mouse Pancreas
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کلمات کلیدی
FVIIIHIF1αhypoxia-inducible factor-1α - عامل القاء شده با هیپوکسی 1αTissue factor - عامل بافتFactor VIII - فاکتور 8Vascular endothelial growth factor - فاکتور رشد اندوتلیال عروقیVascular Endothelial Growth Factor (VEGF) - فاکتور رشد اندوتلیال عروقی (VEGF)Fibrinogen - فیبرینوژنBlood clotting - لخته شدن خونMouse model - مدل موشAcute pancreatitis - پانکراتیت حاد
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
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چکیده انگلیسی
We investigated whether intrapancreatic coagulation, with deposition of the fibrinogen-γ dimer (Fib-γD) and hypoxia, affect the severity of acute pancreatitis (AP) in mice. Pancreata of mice with AP induced by administration of cerulein or by L-arginine, or from patients with pancreatitis, had increased deposition of Fib-γD compared with control pancreata. Heparin administration protected mice from cerulein-induced AP and prevented Fib-γD formation. Cerulein administration resulted in activation and stabilization of hypoxia-inducible factor-1α (HIF1α) in pancreata of oxygen-dependent degradation domain-luciferase HIF1α reporter mice. Cerulein also led to induction of genes regulated by HIF1α, including Vegfa and Ero1a, before evidence of Fib-γD deposition or histologic features of AP. Expression of tissue factor, which is regulated by vascular endothelial growth factor, also increased following cerulein administration. Mice with acinar cell-specific disruption of Hif1a (Hif1aAc-/-) developed spontaneous endoplasmic reticulum stress and less severe AP, but did not accumulate Fib-γD following administration of cerulein. Feeding mice increased pancreatic expression of HIF1α, indicating a physiologic role in the exocrine pancreas. Therefore, HIF1α has bifunctional roles, in exocrine pancreas homeostasis and progression of AP that is promoted by intrapancreatic coagulation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 154, Issue 6, May 2018, Pages 1630-1634.e3
Journal: Gastroenterology - Volume 154, Issue 6, May 2018, Pages 1630-1634.e3
نویسندگان
Min-Jung Park, Sapna Iyer, Xiang Xue, Juliana Bragazzi Cunha, Shufang Gu, David Moons, Steven W. Pipe, John A. Williams, Diane M. Simeone, Yatrik M. Shah, M. Bishr Omary,