The Advances of Application of JAK/STAT Signal Transduction Pathways in Severe Acute Pancreatitis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 WANGGuo-liang ¹ ,  DUIDan-hua ²

1. Department of Hepatobiliary Surgery, Guizhou Provincial People's Hospital, Guiyang 550002, Guizhou Province, China;
2. Department of General Surgery, Zunyi Medical University, Zunyi 563000, Guizhou Province, China;

Corresponding author：

DUIDan-hua, Email: 2361169015@qq.com

Keywords：

JAK/STAT signal transduction pathways; Severe acute pancreatitis; Review

DOI：

10.7507/1007-9424.20150012

Video：

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Objective To summary the advances of application of JAK/STAT signal transduction pathways in severe acute pancreatitis (SAP). Methods By using the method of literature review, the relevant literatures on JAK/STAT signal transduction pathway and its role in various organs damage of SAP were reviewed. Results In the early of SAP, due to the pancreatic acinar cells were damaged, lead to the pancreatic enzyme release, then caused the local inflammatory mediators such as cytokines release, activated the JAK/STAT signal transduction pathways, and through the cascade effect with other signaling pathways further lead to the greater amounts of the release of inflammatory mediators, and that caused the systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Conclusions The JAK/STAT signal transduction pathway may be the key factor of cytokine waterfall cascade reaction process in SAP. Inhibition of this pathway may be a new measure to control the "inflammatory reaction waterfall" in treatment SAP.

Citation： WANGGuo-liang, DUIDan-hua. The Advances of Application of JAK/STAT Signal Transduction Pathways in Severe Acute Pancreatitis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2015, 22(1): 45-49. doi: 10.7507/1007-9424.20150012 Copy

1.	Zyromski N, Murr MM. Evolving concepts in the pathophysiology of acute pancreatitis. Surgery, 2003, 133(3):235-237.
2.	贺宏英. JAK/STAT信号转导途径研究新进展.新医学, 2009, 40(12):827-830.
3.	Espert L, Dusanter-Fourt I, Chelbi-Alix MK. Negative regulation of the JAK/STAT:pathway implication in tumorigenesis. Bull Cancer, 2005, 92(10):845-857.
4.	Rawlings JS, Rosier KM, Harrison DA. The JAK/STAT signaling pathway. J Cell Sci, 2004, 117(Pt 8): 1281-1283.
5.	Schmidt D, Muller S. PIAS/SUMO:new partners in transcriptional regulation. Cell Mol Life Sci, 2003, 60(12):2561-2574.
6.	Held TK, Weihua X, Yuan L, et al. Gamma interferon augments macrophage activation by lipopolysaccharide by two distinct mechanisms at the signal transduction level and via an autocrine mechanism involving tumor necrosis factor alpha and interleukin-1. Infect Immun, 1999, 67(1):206-212.
7.	Kumano K, Nakao A, Nakajima H, et al. Blockade of JAK2 by tyrphostin AG-490 inhibits antigen-induced eosinophil recruitment into the mouse airways. Biochem Biophys Res Commun, 2000, 270(1):209-214.
8.	Cheng HY, Li P, David M, et al. Arsenic inhibition of the JAK/STAT pathway. Oncogene, 2004, 23(20):3603-3612.
9.	Ungureanu D, Saharinen P, Junttila I, et al. Regulation of Jak2 through the ubiquitin-proteasome pathway involves phosphorylation of Jak2 on Y1007 and interaction with SOCS-1. Mol Cell Biol, 2002, 22(10):3316-3326.
10.	Baeg GH, Zhou R, Perrimon N. Genome-wide RNAi analysis of JAK/STAT signaling components in Drosophila. Genes Dev, 2005, 19(16):1861-1870.
11.	Gallmeier E, Schfer C, Moubarak P, et al. JAK and STAT proteins are expressed and activated by IFN-gamma in rat pancreatic acinar cells. Cell Physiol, 2005, 203(1):209-216.
12.	Sampath D, Castro M, Look DC, et al. Constitutive activation of an epithelial signal transducer and activator of t ranscription(STAT) pathway in asthma. J Clin Invest, 1999, 103 (9):1353-1361.
13.	Robinson K, Vona-Davis L, Riggs D, et al. Peptide YY attenuates STAT1-and STAT3 activation induced by TNF-alpha in acinar cell line AR42J. J Am Coll Surg, 2006, 202(5):788-796.
14.	王顺昌, 陈纪伟, 梁冲. FGF-2和STAT-3在小鼠急性胰腺炎组织中的表达及意义.山东医药, 2007, 47(29):31-32.
15.	李敏利, 许小兵, 王彬, 等.促炎因子在实验性重症急性胰腺炎早期对JAK2/STAT3信号通路的影响.安徽医科大学学报, 2014, 49(10):1392-1395.
16.	郝顺心, 沈新明, 吴瑞乔, 等. JAK/STAT通路对急性坏死性胰腺炎大鼠胰腺组织TNF-α表达的影响.中华胰腺外科杂志, 2013, 13(3):199-200.
17.	郑振江, 向光明, 刘续宝.胰腺星状细胞在胰腺纤维化中的作用.中国普外基础与临床杂志, 2010, 17(8):876-879.
18.	Steer ML. Relationship between pancreatits and lung diseases. Respir Physiol, 2001, 128(1):13-161.
19.	Severgnini M, Takahashi S, Rozo LM, et al. Activation of the STAT pathway in acute lung injury. Am J Physiol Lung Cell Mol Physiol, 2004, 286(6):L1282-L1292.
20.	Keyun Shi, Jianzhong Jiang, Tieliang Ma, et al. Dexamethasone attenuates bleomycin-induced lung fibrosis in mice through TGF-β, Smad3 and JAK-STAT pathway. Int J Clin Exp Med, 2014, 7(9):2645-2650.
21.	Chao KC, Chao KF, Chuang CC, et al. Blockade of int erleukin 6 accelerates acinar cell apoptosis and at tenuat es experiment al acute pancreatit is in vivo. Br J Surg, 2006, 93(3):332-338.
22.	李敏利, 朱人敏, 张晓华, 等. Jak2/Stat3信号通路在重症急性胰腺炎大鼠肺损伤中的作用.解放军医学杂志, 2011, 36(6):611-613.
23.	Zyromski N, Murr MM. Evolving concepts in the pathophysiology ofacute pancreatitis. Surgery, 2003, 133(3):235-237.
24.	Murr MM, Yang J, Fier A, et al. Regulation of Kupffer cell TNF gene expression during experimental acute pancreatitis:the role of p382MAPK, ERK1/2, SAPK/JNK, and NF-kappaB. Gastrointest Surg, 2003, 7(1):20-25.
25.	Mota R, Sanchez-Bueno F, Berenguer Pina JJ, et al. Therapeutic treatment with poly (ADP-ribose) polymerase inhibitors attenuates the severity of acute pancreatitis and associated liver and lung injury. Br J Pharmacol, 2007, 151(7):998-1005.
26.	Chan YC, Leung PS. Acute pancreatitis:animal models and recent advances in basic research. Pancreas, 2007, 34 (1):1-14.
27.	桂水清, 罗旭.急性胰腺炎合并肝损害的临床分析.河北医学, 2009, 7(15):790-792.
28.	李敏利, 张晓华, 杨妙芳, 等. JAK/STAT信号通路在胰弹性蛋白酶诱导大鼠Kupffer细胞分泌促炎因子中的作用.解放军医学杂志, 2008, 33(10):1167-1169.
29.	张健, 帅朝霞, 胡志刚, 等. JAK/STAT通路在脂多糖诱导肝细胞HMGB1释放中的作用.南京医科大学学报:自然科学版, 2009, 29(11):1514-1516.
30.	郭婧芸, 朱人敏, 张晓华, 等.抑制JAK/STAT信号通路对实验性急性胰腺炎大鼠肝损伤的保护作用.胃肠病学, 2008, 13(12):719-722.
31.	潘金, 琚坚. JAK/STAT信号转导通路在肝纤维化形成中的作用.临床肝胆病杂志, 2013, 29(5):393-396.
32.	王卫真, 孟明辉, 孔丽, 等. Jak/Stat信号通路在经典CCl4大鼠肝纤维化模型中的动态变化及扶正化瘀方对其影响.临床肝胆病杂志, 2014, 30(4):344-348.
33.	Coopersmith CM, Chang KC, Swanson PE, et al. Overexpression of Bcl-2 in the intestinal epithelium improves survival in septic mice. Crit Care Med, 2002, 30(1):195-201.
34.	周静, 王杉, 安友仲, 等. STAT3在急性重症胰腺炎大鼠肠黏膜屏障功能障碍中的作用.中华普通外科杂志, 2005, 20(3):167-170.
35.	Wig JD, Kochhar R, Ray JD, et al. Endotoxemia predicts outcome in acute pancreatitis. Clin Gastroenterol, 1998, 2(6):121-124.
36.	Held TK, Weihua X, Yuan L, et al. Gamma interferon augments macrophage activation by lipopolysaccharide by two distinct mechanisms at the signal transduction level and via an autocrine mechanisminvolving tumor necrosis factor alpha and interleukin-1. Infect Immun, 1999, 67(1):206-212.
37.	Fridman JS, Scherle PA, Collins R, et al. Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis:preclinical characterization of INCB028050. J Immunol, 2010, 184(9):5298-5307.
38.	靳远萌. JAK/STAT通路在肾间质纤维化中的进展.肾脏病与透析肾移植志, 2012, 21(3):31-33.
39.	李敏利, 张晓华, 朱人敏, 等.抑制JAK/STAT3信号通路对重症急性胰腺炎肾损伤的保护作用.世界华人消化杂志, 2011, 19(32):3297-3301.
40.	杨恒, 吕和平, 周蒙滔, 等.丙酮酸乙酯对大鼠重症急性胰腺炎肾损伤的保护作用.肝胆胰外科杂志, 2011, 23(2):89-95.
41.	王国良, 兑丹华, 白亮, 等. TAP诱导大鼠胰腺腺泡细胞释放HMGB1的研究.中国普外基础与临床杂志, 2012, 19(10):1074-1078.
42.	刘尧, 兑丹华, 王玲.高迁徙率族蛋白1在急性胰腺炎大鼠中的表达及其意义.中华实验外科杂志, 2012, 29(10):2041-2044.
43.	任浩源, 兑丹华, 刘尧, 等. Janus激酶2/信号转导与转录激活子3信号通路在胰蛋白酶原激活肽诱导大鼠胰腺腺泡细胞释放高迁移率族蛋白B1中的作用.中华实验外科杂志, 2014, 31(7):1511-1513.

1. Zyromski N, Murr MM. Evolving concepts in the pathophysiology of acute pancreatitis. Surgery, 2003, 133(3):235-237.
2. 贺宏英. JAK/STAT信号转导途径研究新进展.新医学, 2009, 40(12):827-830.
3. Espert L, Dusanter-Fourt I, Chelbi-Alix MK. Negative regulation of the JAK/STAT:pathway implication in tumorigenesis. Bull Cancer, 2005, 92(10):845-857.
4. Rawlings JS, Rosier KM, Harrison DA. The JAK/STAT signaling pathway. J Cell Sci, 2004, 117(Pt 8): 1281-1283.
5. Schmidt D, Muller S. PIAS/SUMO:new partners in transcriptional regulation. Cell Mol Life Sci, 2003, 60(12):2561-2574.
6. Held TK, Weihua X, Yuan L, et al. Gamma interferon augments macrophage activation by lipopolysaccharide by two distinct mechanisms at the signal transduction level and via an autocrine mechanism involving tumor necrosis factor alpha and interleukin-1. Infect Immun, 1999, 67(1):206-212.
7. Kumano K, Nakao A, Nakajima H, et al. Blockade of JAK2 by tyrphostin AG-490 inhibits antigen-induced eosinophil recruitment into the mouse airways. Biochem Biophys Res Commun, 2000, 270(1):209-214.
8. Cheng HY, Li P, David M, et al. Arsenic inhibition of the JAK/STAT pathway. Oncogene, 2004, 23(20):3603-3612.
9. Ungureanu D, Saharinen P, Junttila I, et al. Regulation of Jak2 through the ubiquitin-proteasome pathway involves phosphorylation of Jak2 on Y1007 and interaction with SOCS-1. Mol Cell Biol, 2002, 22(10):3316-3326.
10. Baeg GH, Zhou R, Perrimon N. Genome-wide RNAi analysis of JAK/STAT signaling components in Drosophila. Genes Dev, 2005, 19(16):1861-1870.
11. Gallmeier E, Schfer C, Moubarak P, et al. JAK and STAT proteins are expressed and activated by IFN-gamma in rat pancreatic acinar cells. Cell Physiol, 2005, 203(1):209-216.
12. Sampath D, Castro M, Look DC, et al. Constitutive activation of an epithelial signal transducer and activator of t ranscription(STAT) pathway in asthma. J Clin Invest, 1999, 103 (9):1353-1361.
13. Robinson K, Vona-Davis L, Riggs D, et al. Peptide YY attenuates STAT1-and STAT3 activation induced by TNF-alpha in acinar cell line AR42J. J Am Coll Surg, 2006, 202(5):788-796.
14. 王顺昌, 陈纪伟, 梁冲. FGF-2和STAT-3在小鼠急性胰腺炎组织中的表达及意义.山东医药, 2007, 47(29):31-32.
15. 李敏利, 许小兵, 王彬, 等.促炎因子在实验性重症急性胰腺炎早期对JAK2/STAT3信号通路的影响.安徽医科大学学报, 2014, 49(10):1392-1395.
16. 郝顺心, 沈新明, 吴瑞乔, 等. JAK/STAT通路对急性坏死性胰腺炎大鼠胰腺组织TNF-α表达的影响.中华胰腺外科杂志, 2013, 13(3):199-200.
17. 郑振江, 向光明, 刘续宝.胰腺星状细胞在胰腺纤维化中的作用.中国普外基础与临床杂志, 2010, 17(8):876-879.
18. Steer ML. Relationship between pancreatits and lung diseases. Respir Physiol, 2001, 128(1):13-161.
19. Severgnini M, Takahashi S, Rozo LM, et al. Activation of the STAT pathway in acute lung injury. Am J Physiol Lung Cell Mol Physiol, 2004, 286(6):L1282-L1292.
20. Keyun Shi, Jianzhong Jiang, Tieliang Ma, et al. Dexamethasone attenuates bleomycin-induced lung fibrosis in mice through TGF-β, Smad3 and JAK-STAT pathway. Int J Clin Exp Med, 2014, 7(9):2645-2650.
21. Chao KC, Chao KF, Chuang CC, et al. Blockade of int erleukin 6 accelerates acinar cell apoptosis and at tenuat es experiment al acute pancreatit is in vivo. Br J Surg, 2006, 93(3):332-338.
22. 李敏利, 朱人敏, 张晓华, 等. Jak2/Stat3信号通路在重症急性胰腺炎大鼠肺损伤中的作用.解放军医学杂志, 2011, 36(6):611-613.
23. Zyromski N, Murr MM. Evolving concepts in the pathophysiology ofacute pancreatitis. Surgery, 2003, 133(3):235-237.
24. Murr MM, Yang J, Fier A, et al. Regulation of Kupffer cell TNF gene expression during experimental acute pancreatitis:the role of p382MAPK, ERK1/2, SAPK/JNK, and NF-kappaB. Gastrointest Surg, 2003, 7(1):20-25.
25. Mota R, Sanchez-Bueno F, Berenguer Pina JJ, et al. Therapeutic treatment with poly (ADP-ribose) polymerase inhibitors attenuates the severity of acute pancreatitis and associated liver and lung injury. Br J Pharmacol, 2007, 151(7):998-1005.
26. Chan YC, Leung PS. Acute pancreatitis:animal models and recent advances in basic research. Pancreas, 2007, 34 (1):1-14.
27. 桂水清, 罗旭.急性胰腺炎合并肝损害的临床分析.河北医学, 2009, 7(15):790-792.
28. 李敏利, 张晓华, 杨妙芳, 等. JAK/STAT信号通路在胰弹性蛋白酶诱导大鼠Kupffer细胞分泌促炎因子中的作用.解放军医学杂志, 2008, 33(10):1167-1169.
29. 张健, 帅朝霞, 胡志刚, 等. JAK/STAT通路在脂多糖诱导肝细胞HMGB1释放中的作用.南京医科大学学报:自然科学版, 2009, 29(11):1514-1516.
30. 郭婧芸, 朱人敏, 张晓华, 等.抑制JAK/STAT信号通路对实验性急性胰腺炎大鼠肝损伤的保护作用.胃肠病学, 2008, 13(12):719-722.
31. 潘金, 琚坚. JAK/STAT信号转导通路在肝纤维化形成中的作用.临床肝胆病杂志, 2013, 29(5):393-396.
32. 王卫真, 孟明辉, 孔丽, 等. Jak/Stat信号通路在经典CCl4大鼠肝纤维化模型中的动态变化及扶正化瘀方对其影响.临床肝胆病杂志, 2014, 30(4):344-348.
33. Coopersmith CM, Chang KC, Swanson PE, et al. Overexpression of Bcl-2 in the intestinal epithelium improves survival in septic mice. Crit Care Med, 2002, 30(1):195-201.
34. 周静, 王杉, 安友仲, 等. STAT3在急性重症胰腺炎大鼠肠黏膜屏障功能障碍中的作用.中华普通外科杂志, 2005, 20(3):167-170.
35. Wig JD, Kochhar R, Ray JD, et al. Endotoxemia predicts outcome in acute pancreatitis. Clin Gastroenterol, 1998, 2(6):121-124.
36. Held TK, Weihua X, Yuan L, et al. Gamma interferon augments macrophage activation by lipopolysaccharide by two distinct mechanisms at the signal transduction level and via an autocrine mechanisminvolving tumor necrosis factor alpha and interleukin-1. Infect Immun, 1999, 67(1):206-212.
37. Fridman JS, Scherle PA, Collins R, et al. Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis:preclinical characterization of INCB028050. J Immunol, 2010, 184(9):5298-5307.
38. 靳远萌. JAK/STAT通路在肾间质纤维化中的进展.肾脏病与透析肾移植志, 2012, 21(3):31-33.
39. 李敏利, 张晓华, 朱人敏, 等.抑制JAK/STAT3信号通路对重症急性胰腺炎肾损伤的保护作用.世界华人消化杂志, 2011, 19(32):3297-3301.
40. 杨恒, 吕和平, 周蒙滔, 等.丙酮酸乙酯对大鼠重症急性胰腺炎肾损伤的保护作用.肝胆胰外科杂志, 2011, 23(2):89-95.
41. 王国良, 兑丹华, 白亮, 等. TAP诱导大鼠胰腺腺泡细胞释放HMGB1的研究.中国普外基础与临床杂志, 2012, 19(10):1074-1078.
42. 刘尧, 兑丹华, 王玲.高迁徙率族蛋白1在急性胰腺炎大鼠中的表达及其意义.中华实验外科杂志, 2012, 29(10):2041-2044.
43. 任浩源, 兑丹华, 刘尧, 等. Janus激酶2/信号转导与转录激活子3信号通路在胰蛋白酶原激活肽诱导大鼠胰腺腺泡细胞释放高迁移率族蛋白B1中的作用.中华实验外科杂志, 2014, 31(7):1511-1513.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

The Advances of Application of JAK/STAT Signal Transduction Pathways in Severe Acute Pancreatitis

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