自噬在急性胰腺炎发生发展中的作用

李春云; 刘瑞霞; 阴赪宏

doi:10.3969/j.issn.1001-5256.2019.05.051

自噬在急性胰腺炎发生发展中的作用

DOI: 10.3969/j.issn.1001-5256.2019.05.051

1. 首都医科大学附属北京妇产医院内科
2. 首都医科大学附属北京妇产医院中心实验室

基金项目:

国家自然科学基金资助项目(81571933)；

详细信息

中图分类号: R576
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- 被引次数: 0
出版历程
- 收稿日期: 2018-11-02
- 出版日期: 2019-05-20

The role of autophagy in the development and progression of acute pancreatitis

Department of Internal Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University

Research funding:

摘要

摘要: 急性胰腺炎(AP)是一种胰腺外分泌部炎症性疾病,其发病的病理生理机制尚不清楚。自噬是细胞内代谢降解的一个重要途径,自噬损伤与许多疾病的发生发展密切相关。近来研究发现,AP中自噬过程发生明显异常,自噬体与溶酶体融合障碍,自噬溶酶体降解功能显著下降。胰腺内胰酶异常激活与炎症反应是启动AP的关键事件,而自噬功能异常与二者皆密切相关。对AP自噬功能障碍的上下游机制进行探究,有助于发现治疗胰腺炎新的分子目标和策略。
- 胰腺炎 /
- 自噬 /
- 溶酶体相关膜糖蛋白质类 /
- 炎症 /
- 综述
Abstract: Acute pancreatitis ( AP) is an exocrine inflammatory disease of the pancreas, the pathophysiological mechanism of AP remains unclear. Autophagy is an important pathway of metabolic degradation in cells, and autophagy impairment is closely associated with the development and progression of many diseases. Recent studies have found that the process of autophagy is abnormal in AP, with impaired fusion of autophagosome and lysosome and a significant reduction in the degradation function of autolysosome. Abnormal activation of pancreatic enzymes and inflammatory response is the key event in the initiation of AP, and abnormal autophagy is closely associated with these two events.The study of the upstream and downstream mechanisms of autophagy dysfunction in AP may help to find new molecular targets and strategies for the treatment of AP.
- pancreatitis /
- autophagy /
- tysosome-associated membrane glycoproteins /
- inflammation /
- review

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参考文献(36)

[1] BANKS PA, BOLLEN TL, DERVENIS C, et al. Classification of acute pancreatitis—2012:Revision of the Atlanta classification and definitions by international consensus[J]. Gut, 2013, 62 (1) :102-111.

[2] SALVADOR P, JAVIER P, LUIS S, et al. Redox signaling in acute pancreatitis[J]. Redox Biol, 2015, 5 (2) :1-14.

[3] YANG S, IMAMURA Y, JENKINS RW, et al. Autophagy inhibition dysregulates TBK1 signaling and promotes pancreatic inflammation[J]. Cancer Immunol Res, 2016, 4 (6) :520-530.

[4] CIECHANOVER A. Proteolysis:From the lysosome to ubiquitin and the proteasome[J]. Nat Rev Mol Cell Biol, 2005, 6 (1) :79-87.

[5] GLICK D, BARTH S, MACLEOD KF. Autophagy:Cellular and molecular mechanisms[J]. J Pathol, 2010, 221 (1) :3-12.

[6] KAUSHIK S, BANDYOPADHYAY U, SRIDHAR S, et al. Chaperone-mediated autophagy at a glance[J]. J Cell Sci, 2011, 124 (4) :495-499.

[7] MIZUSHIMA N, YOSHIMORI T, OHSUMI Y. The role of Atg proteins in autophagosome formation[J]. Annu Rev Cell Dev Biol, 2011, 27 (1) :107-132.

[8] SAFTIG P, KLUMPERMAN J. Lysosome biogenesis and lysosomal membrane proteins:Trafficking meets function[J]. Nat Rev Mol Cell Biol, 2009, 10 (9) :623-635.

[9] BRAULKE T, BONIFACINO JS. Sorting of lysosomal proteins[J]. Biochim Biophys Acta, 2009, 1793 (4) :605-614.

[10] STAPPENBECK TS, RIOUX JD, MIZOGUCHI A, et al. Crohn disease:A current perspective on genetics, autophagy and immunity[J]. Autophagy, 2011, 7 (4) :355-374.

[11] KLIONSKY DJ, ABDELMOHSEN K, ABE A, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) [J]. Autophagy, 2016, 12 (1) :1-222.

[12] GUKOVSKY I, GUKOVSKAYA AS. Impaired autophagy underlies key pathological responses of acute pancreatitis[J]. Autophagy, 2010, 6 (3) :428-429.

[13] GUKOVSKY I, PANDOL SJ, MARENINOVA OA, et al. Impaired autophagy and organellar dysfunction in pancreatitis[J]. J Gastroenterol Hepatol, 2012, 27 (2) :27-32.

[14] MARENINOVA OA, HERMANN K, FRENCH SW, et al. Impaired autophagic flux mediates acinar cell vacuole formation and trypsinogen activation in rodent models of acute pancreatitis[J]. J Clin Invest, 2009, 119 (11) :3340-3355.

[15] KLAUSS S, SCHORN S, TELLER S, et al. Genetically induced vs. classical animal models of chronic pancreatitis:A critical comparison[J]. FASEB J, 2018.[Epub ahead of print].

[16] IWAHASHI K, HIKITA H, MAKINO Y, et al. Autophagy impairment in pancreatic acinar cells causes zymogen granule accumulation and pancreatitis[J]. Biochem Biophys Res Commun, 2018, 503 (4) :2576-2582.

[17] MARENINOVA OA, SENDLER M, MALLA SR, et al. Lysosome associated membrane proteins maintain pancreatic acinar cell homeostasis:LAMP-2 deficient mice develop pancreatitis[J]. Cell Mol Gastroenterol Hepatol, 2015, 1 (6) :678-694.

[18] ZHU HW, YU X, ZHU SH, et al. The fusion of autophagosome with lysosome is impaired in L-arginine-induced acute pancreatitis[J]. Int J Clin Exp Pathol, 2015, 8 (9) :11164-11170.

[19] STEER ML. Early events in acute pancreatitis[J]. Baillieres Best Pract Res Clin Gastroenterol, 1999, 13 (2) :213-225.

[20] BOONEN M, van MEEL E, OORSCHOT V, et al. Vacuolization of mucolipidosis type II mouse exocrine gland cells represents accumulation of autolysosomes[J]. Mol Biol Cell, 2011, 22 (8) :1135-1147.

[21] GUKOVSKY I, LI N, TODORIC J, et al. Inflammation, autophagy, and obesity:Common features in the pathogenesis of pancreatitis and pancreatic cancer[J]. Gastroenterology, 2013, 144 (6) :1199-1209.

[22] HASHIMOTO D, OHMURAYA M, HIROTA M, et al. Involvement of autophagy in trypsinogen activation within the pancreatic acinar cells[J]. J Cell Biol, 2008, 181 (7) :1065-1072.

[23] SAH RP, DUDEJA V, DAWRA RK, et al. Cerulein-induced chronic pancreatitis does not require intra-acinar activation of trypsinogen in mice[J]. Gastroenterology, 2013, 144 (5) :1076-1085.

[24] VOJO D, TATSUYA S, SHIZUO A. Autophagy in infection, inflammation, and immunity[J]. Nat Rev Immunol, 2013, 13 (10) :722-737.

[25] FENG Y, CUI Y, GAO JL, et al. Resveratrol attenuates neuronal autophagy and inflammatory injury by inhibiting the TLR4/NF-κB signaling pathway in experimental traumatic brain injury[J]. Int J Mol Med, 2016, 37 (4) :921-930.

[26] YANG S, BING M, CHEN F, et al. Autophagy regulation by the nuclear factorκB signal axis in acute pancreatitis[J]. Pancreas, 2012, 41 (3) :367-373.

[27] WANG X, ZHOU G, LIU C, et al. Acanthopanax versus 3-Methyladenine ameliorates sodium taurocholate-induced severe acute pancreatitis by inhibiting the autophagic pathway in rats[J]. Mediators Inflamm, 2016, 2016:8369704.

[28] WAN J, CHEN J, WU D, et al. Regulation of autophagy affects the prognosis of mice with severe acute pancreatitis[J].Dig Dis Sci, 2018, 63 (10) :2639-2650.

[29] HUANG L, JIANG Y, SUN Z, et al. Autophagy strengthens intestinal mucosal barrier by attenuating oxidative stress in severe acute pancreatitis[J]. Dig Dis Sci, 2018, 63 (4) :910-919.

[30] GUKOVSKAYA AS, GUKOVSKY I. Autophagy and pancreatitis[J]. Am J Physiol Gastrointest Liver Physiol, 2012, 303 (9) :g993-g1003.

[31] MEISTER T, NIEHUES R, HAHN D, et al. Missorting of cathepsin B into the secretory compartment of CI-MPR/IGFIIdeficient mice does not induce spontaneous trypsinogen activation but leads to enhanced trypsin activity during experimental pancreatitis—without affecting disease severity[J]. J Physiol Pharmacol, 2010, 61 (5) :565-575.

[32] WAN JH, CHEN J, WU DY, et al. Regulation of autophagy affects the prognosis of mice with severe acute pancreatitis[J].Dig Dis Sci, 2018, 63 (10) :2639-2650.

[33] SONG ZG, HUANG YM, LIU C, et al. miR-352 participates in the regulation of trypsinogen activation in pancreatic acinar cells by influencing the function of autophagic lysosomes[J].Oncotarget, 2018, 9 (13) :10868-10879.

[34] ZHU MD, LUO YQ. Research advances in integrated traditional Chinese and Western medicine therapy for severe acute pancreatitis[J]. J Clin Hepatol, 2017, 33 (1) :188-193. (in Chinese) 朱美冬, 罗运权.中西医治疗重症急性胰腺炎的研究进展[J].临床肝胆病杂志, 2017, 33 (1) :188-193.

[35] YU XZ, LI CY, SONG HC, et al. Emodin attenuates autophagy response to protect the pancreas from acute pancreatitis failure[J]. Pancreas, 2018, 47 (7) :892-897.

[36] WANG XH, ZHOU GX, LIU C, et al. Acanthopanax versus 3-methyladenine ameliorates sodium taurocholate-induced severe acute pancreatitis by inhibiting the autophagic pathway in rats[J]. Mediators Inflamm, 2016, 2016:8369704.

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