Autophagy, Acute Pancreatitis and the Metamorphoses of a Trypsinogen-Activating Organelle.

Autophagy, Acute Pancreatitis and the Metamorphoses of a Trypsinogen-Activating Organelle.
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DOI:
10.3390/cells11162514
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发表时间:
2022-08-12
期刊:
影响因子:
6
通讯作者:
Tepikin, Alexei
Tepikin, Alexei
中科院分区:
生物学2区
文献类型:
--
作者:
Voronina, Svetlana;Chvanov, Michael;De Faveri, Francesca;Mayer, Ulrike;Wileman, Tom;Criddle, David;Tepikin, Alexei

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最近的研究强调了自噬的重要性,特别是非典型自噬在急性胰腺炎(一种常见的疾病,具有相当大的发病率和显著的死亡率)的发展和进展。急性胰腺炎发展中的一个重要早期事件是胰蛋白酶原的胰腺内激活,(即,胰蛋白酶的形成)导致器官的自身消化。另一个与该病发生相关的突出现象是空泡化,特别是在胰腺腺泡细胞中形成巨大的内吞空泡。这些细胞器在暴露于几种急性胰腺炎诱导物(包括牛磺石胆酸和高浓度促分泌素胆囊收缩素和乙酰胆碱)的腺泡细胞中发育。值得注意的是,早期胰蛋白酶原激活发生在内吞空泡中。这些胰蛋白酶原活化细胞器经历活化、长距离运输和非典型自噬。在这篇综述中,我们将讨论自噬在急性胰腺炎中的作用,特别是最近发现的内吞空泡的LAP样非经典自噬(LNCA)。
Recent studies have highlighted the importance of autophagy and particularly non-canonical autophagy in the development and progression of acute pancreatitis (a frequent disease with considerable morbidity and significant mortality). An important early event in the development of acute pancreatitis is the intrapancreatic activation of trypsinogen, (i.e., formation of trypsin) leading to the autodigestion of the organ. Another prominent phenomenon associated with the initiation of this disease is vacuolisation and specifically the formation of giant endocytic vacuoles in pancreatic acinar cells. These organelles develop in acinar cells exposed to several inducers of acute pancreatitis (including taurolithocholic acid and high concentrations of secretagogues cholecystokinin and acetylcholine). Notably, early trypsinogen activation occurs in the endocytic vacuoles. These trypsinogen-activating organelles undergo activation, long-distance trafficking, and non-canonical autophagy. In this review, we will discuss the role of autophagy in acute pancreatitis and particularly focus on the recently discovered LAP-like non-canonical autophagy (LNCA) of endocytic vacuoles.
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