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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Abstract Full text Figures/Tables Video References Cited by

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.	賀宏英. JAK/STAT信號轉導途徑研究新進展.新醫學, 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.	王順昌, 陳紀偉, 梁沖. FGF-2和STAT-3在小鼠急性胰腺炎組織中的表達及意義.山東醫藥, 2007, 47(29):31-32.
15.	李敏利, 許小兵, 王彬, 等.促炎因子在實驗性重癥急性胰腺炎早期對JAK2/STAT3信號通路的影響.安徽醫科大學學報, 2014, 49(10):1392-1395.
16.	郝順心, 沈新明, 吳瑞喬, 等. JAK/STAT通路對急性壞死性胰腺炎大鼠胰腺組織TNF-α表達的影響.中華胰腺外科雜志, 2013, 13(3):199-200.
17.	鄭振江, 向光明, 劉續寶.胰腺星狀細胞在胰腺纖維化中的作用.中國普外基礎與臨床雜志, 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, 張曉華, 等. Jak2/Stat3信號通路在重癥急性胰腺炎大鼠肺損傷中的作用.解放軍醫學雜志, 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, 羅旭.急性胰腺炎合并肝損害的臨床分析.河北醫學, 2009, 7(15):790-792.
28.	李敏利, 張曉華, 楊妙芳, 等. JAK/STAT信號通路在胰彈性蛋白酶誘導大鼠Kupffer細胞分泌促炎因子中的作用.解放軍醫學雜志, 2008, 33(10):1167-1169.
29.	張健, 帥朝霞, 胡志剛, 等. JAK/STAT通路在脂多糖誘導肝細胞HMGB1釋放中的作用.南京醫科大學學報:自然科學版, 2009, 29(11):1514-1516.
30.	郭婧蕓, 朱人敏, 張曉華, 等.抑制JAK/STAT信號通路對實驗性急性胰腺炎大鼠肝損傷的保護作用.胃腸病學, 2008, 13(12):719-722.
31.	潘金, 琚堅. JAK/STAT信號轉導通路在肝纖維化形成中的作用.臨床肝膽病雜志, 2013, 29(5):393-396.
32.	王衛真, 孟明輝, 孔麗, 等. Jak/Stat信號通路在經典CCl4大鼠肝纖維化模型中的動態變化及扶正化瘀方對其影響.臨床肝膽病雜志, 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.	周靜, 王杉, 安友仲, 等. STAT3在急性重癥胰腺炎大鼠腸黏膜屏障功能障礙中的作用.中華普通外科雜志, 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.	靳遠萌. JAK/STAT通路在腎間質纖維化中的進展.腎臟病與透析腎移植志, 2012, 21(3):31-33.
39.	李敏利, 張曉華, 朱人敏, 等.抑制JAK/STAT3信號通路對重癥急性胰腺炎腎損傷的保護作用.世界華人消化雜志, 2011, 19(32):3297-3301.
40.	楊恒, 呂和平, 周蒙滔, 等.丙酮酸乙酯對大鼠重癥急性胰腺炎腎損傷的保護作用.肝膽胰外科雜志, 2011, 23(2):89-95.
41.	王國良, 兌丹華, 白亮, 等. TAP誘導大鼠胰腺腺泡細胞釋放HMGB1的研究.中國普外基礎與臨床雜志, 2012, 19(10):1074-1078.
42.	劉堯, 兌丹華, 王玲.高遷徙率族蛋白1在急性胰腺炎大鼠中的表達及其意義.中華實驗外科雜志, 2012, 29(10):2041-2044.
43.	任浩源, 兌丹華, 劉堯, 等. Janus激酶2/信號轉導與轉錄激活子3信號通路在胰蛋白酶原激活肽誘導大鼠胰腺腺泡細胞釋放高遷移率族蛋白B1中的作用.中華實驗外科雜志, 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. 賀宏英. JAK/STAT信號轉導途徑研究新進展.新醫學, 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. 王順昌, 陳紀偉, 梁沖. FGF-2和STAT-3在小鼠急性胰腺炎組織中的表達及意義.山東醫藥, 2007, 47(29):31-32.
15. 李敏利, 許小兵, 王彬, 等.促炎因子在實驗性重癥急性胰腺炎早期對JAK2/STAT3信號通路的影響.安徽醫科大學學報, 2014, 49(10):1392-1395.
16. 郝順心, 沈新明, 吳瑞喬, 等. JAK/STAT通路對急性壞死性胰腺炎大鼠胰腺組織TNF-α表達的影響.中華胰腺外科雜志, 2013, 13(3):199-200.
17. 鄭振江, 向光明, 劉續寶.胰腺星狀細胞在胰腺纖維化中的作用.中國普外基礎與臨床雜志, 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, 張曉華, 等. Jak2/Stat3信號通路在重癥急性胰腺炎大鼠肺損傷中的作用.解放軍醫學雜志, 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, 羅旭.急性胰腺炎合并肝損害的臨床分析.河北醫學, 2009, 7(15):790-792.
28. 李敏利, 張曉華, 楊妙芳, 等. JAK/STAT信號通路在胰彈性蛋白酶誘導大鼠Kupffer細胞分泌促炎因子中的作用.解放軍醫學雜志, 2008, 33(10):1167-1169.
29. 張健, 帥朝霞, 胡志剛, 等. JAK/STAT通路在脂多糖誘導肝細胞HMGB1釋放中的作用.南京醫科大學學報:自然科學版, 2009, 29(11):1514-1516.
30. 郭婧蕓, 朱人敏, 張曉華, 等.抑制JAK/STAT信號通路對實驗性急性胰腺炎大鼠肝損傷的保護作用.胃腸病學, 2008, 13(12):719-722.
31. 潘金, 琚堅. JAK/STAT信號轉導通路在肝纖維化形成中的作用.臨床肝膽病雜志, 2013, 29(5):393-396.
32. 王衛真, 孟明輝, 孔麗, 等. Jak/Stat信號通路在經典CCl4大鼠肝纖維化模型中的動態變化及扶正化瘀方對其影響.臨床肝膽病雜志, 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. 周靜, 王杉, 安友仲, 等. STAT3在急性重癥胰腺炎大鼠腸黏膜屏障功能障礙中的作用.中華普通外科雜志, 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. 靳遠萌. JAK/STAT通路在腎間質纖維化中的進展.腎臟病與透析腎移植志, 2012, 21(3):31-33.
39. 李敏利, 張曉華, 朱人敏, 等.抑制JAK/STAT3信號通路對重癥急性胰腺炎腎損傷的保護作用.世界華人消化雜志, 2011, 19(32):3297-3301.
40. 楊恒, 呂和平, 周蒙滔, 等.丙酮酸乙酯對大鼠重癥急性胰腺炎腎損傷的保護作用.肝膽胰外科雜志, 2011, 23(2):89-95.
41. 王國良, 兌丹華, 白亮, 等. TAP誘導大鼠胰腺腺泡細胞釋放HMGB1的研究.中國普外基礎與臨床雜志, 2012, 19(10):1074-1078.
42. 劉堯, 兌丹華, 王玲.高遷徙率族蛋白1在急性胰腺炎大鼠中的表達及其意義.中華實驗外科雜志, 2012, 29(10):2041-2044.
43. 任浩源, 兌丹華, 劉堯, 等. Janus激酶2/信號轉導與轉錄激活子3信號通路在胰蛋白酶原激活肽誘導大鼠胰腺腺泡細胞釋放高遷移率族蛋白B1中的作用.中華實驗外科雜志, 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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