Models of acute and chronic pancreatitis

Gastroenterology

Volumn 144, Issue 6, 2013, Pages 1180-1193

  Lerch, Markus M ^a   Gorelick, Fred S ^b  

^a UNIVERSITY MEDICINE GREIFSWALD   (Germany)

^b YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Caerulein; Pathogenesis; Pathophysiology; Trypsin

Indexed keywords

ACETYLCHOLINE; AQUAPORIN 1; ARGININE; CERULETIDE; CHOLECYSTOKININ; CIGARETTE SMOKE; COLLAGEN TYPE 3; CYCLOOXYGENASE 2; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; FIBRONECTIN; INTERLEUKIN 10; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; SERINE PROTEINASE INHIBITOR; TOLL LIKE RECEPTOR 4; TRANSFORMING GROWTH FACTOR BETA1; TUMOR NECROSIS FACTOR ALPHA;

ACETYLCHOLINE RELEASE; ACINAR CELL; ACUTE PANCREATITIS; ARTHUS PHENOMENON; AUTOIMMUNE PANCREATITIS; CALCIUM SIGNALING; CELL ACTIVATION; CELL ORGANELLE; CHOLELITHIASIS; CHOLESTASIS; CHRONIC PANCREATITIS; CONCENTRATION (PARAMETERS); CYSTIC FIBROSIS; DIETARY INTAKE; DISEASE COURSE; DISEASE SEVERITY; ENDOPLASMIC RETICULUM; ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY; EXTRACELLULAR CALCIUM; EXTRACELLULAR MATRIX; GENE TRANSFER; GENETIC MANIPULATION; GENETIC VARIABILITY; HUMAN; IMMUNE RESPONSE; INTRACELLULAR SIGNALING; NONHUMAN; PANCREAS DUCT STENOSIS; PANCREAS SECRETION; PANCREATITIS; PHENOTYPE; PRIORITY JOURNAL; REVIEW; SECRETORY VESICLE; SIGNAL TRANSDUCTION; STIMULUS SECRETION COUPLING;

EID: 84876788888     PISSN: 00165085     EISSN: 15280012     Source Type: Journal    
DOI: 10.1053/j.gastro.2012.12.043     Document Type: Article

References (147)

1. C. Benard Leçon de Physilogie Experimentale 1856 Bailliere Paris
2. T. Hirano, A. Saluja, P. Ramarao Apical secretion of lysosomal enzymes in rabbit pancreas occurs via a secretagogue regulated pathway and is increased after pancreatic duct obstruction J Clin Invest 87 1991 865 869
3. M.M. Lerch, A.K. Saluja, R. Dawra Acute necrotizing pancreatitis in the opossum: earliest morphological changes involve acinar cells Gastroenterology 103 1992 205 213
4. J. Mouret Contribution a l'etude des cellules glandulaires (pancreas) Anat Physiol 31 1895 221 236
5. M. Lampel, H. Kern Acute interstitial pancreatitis in the rat induced by excessive doses of pancreatic secretagogue Virchows Arch A Pathol Anat Histol 373 1977 97 117
6. G. Adler, C. Hahn, H.F. Kern Caerulein-induced pancreatitis in rats: increased lysosomal enzyme activity and autophagocytosis Digestion 32 1985 10 18
7. A. Saluja, I. Saito, M. Saluja In vivo rat pancreatic acinar cell function during supramaximal stimulation with caerulein Am J Physiol 249 1985 G702 G710
8. H. Helin, M. Mero, H. Markkula Pancreatic acinar ultrastructure in human acute pancreatitis Virchows Arch A Pathol Anat Histol 387 1980 259 270
9. C. Niederau, C.D. Ferrell, J.H. Grendell Caerulein-induced acute necrotizing pancreatitis in mice: protective effects of proglumide, benzotript, and secretin Gastroenterology 88 1985 1192 1204
10. H. Yamaguchi, T. Kimura, K. Mimura Activation of proteases in caerulein-induced pancreatitis Pancreas 4 1989 565 571
11. H. Chiari Über die selbstverdauung des menschlichen pankreas 17 1896 Ztschr f Heilk Berlin 69 96
12. D.C. Whitcomb, M.C. Gorry, R.A. Preston Hereditary pancreatitis is caused by a mutation on the cationic trypsinogen gene Nat Genet 14 1996 141 145
13. I. Ellis, M.M. Lerch, D.C. Whitcomb Genetic testing for hereditary pancreatitis: guidelines for indications, counselling, consent and privacy issues Pancreatology 1 2001 405 415
14. H. Witt, W. Luck, H.C. Hennies Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis Nat Genet 25 2000 213 216
15. C. Bartholomew Acute scorpion pancreatitis in Trinidad Br Med J 1 1970 666 668
16. S. Singh, U. Bhardwaj, S.K. Verma Hyperamylasemia and acute pancreatitis following anticholinesterase poisoning Hum Exp Toxicol 26 2007 467 471
17. G. Roeyen, T. Chapelle, P. Jorens Necrotizing pancreatitis due to poisoning with organophosphate pesticides Acta Gastroenterol Belg 71 2008 27 29
18. B. Becerril, S. Marangoni, L.D. Possani Toxins and genes isolated from scorpions of the genus Tityus Toxicon 35 1997 821 835
19. P.L. Fletcher Jr, M.D. Fletcher, L.D. Possani Characteristics of pancreatic exocrine secretion produced by venom from the Brazilian scorpion, Tityus serrulatus Eur J Cell Biol 58 1992 259 270
20. M.M. Lerch, F.S. Gorelick Early trypsinogen activation in acute pancreatitis Med Clin North Am 84 2000 549 563 viii
21. R. Dawra, R.P. Sah, V. Dudeja Intra-acinar trypsinogen activation mediates early stages of pancreatic injury but not inflammation in mice with acute pancreatitis Gastroenterology 141 2011 2210 2217.e2
22. W. Halangk, B. Kruger, M. Ruthenburger Trypsin activity is not involved in premature, intrapancreatic trypsinogen activation Am J Physiol Gastrointest Liver Physiol 282 2002 G367 G374
23. B. Ji, Y. Bi, D. Simeone Human pancreatic acinar cells lack functional responses to cholecystokinin and gastrin Gastroenterology 121 2001 1380 1390
24. J.A. Murphy, D.N. Criddle, M. Sherwood Direct activation of cytosolic Ca2+ signaling and enzyme secretion by cholecystokinin in human pancreatic acinar cells Gastroenterology 135 2008 632 641
25. O.A. Mareninova, K.F. Sung, P. Hong Cell death in pancreatitis: caspases protect from necrotizing pancreatitis J Biol Chem 281 2006 3370 3381
26. O.A. Mareninova, K. Hermann, S.W. French Impaired autophagic flux mediates acinar cell vacuole formation and trypsinogen activation in rodent models of acute pancreatitis J Clin Invest 119 2009 3340 3355
27. A. Abdulla, D. Awla, H. Thorlacius Role of neutrophils in the activation of trypsinogen in severe acute pancreatitis J Leukoc Biol 90 2011 975 982
28. A.S. Gukovskaya, E. Vaquero, V. Zaninovic Neutrophils and NADPH oxidase mediate intrapancreatic trypsin activation in murine experimental acute pancreatitis Gastroenterology 122 2002 974 984
29. M. Sendler, A. Dummer, F.U. Weiss Tumour necrosis factor alpha secretion induces protease activation and acinar cell necrosis in acute experimental pancreatitis in mice Gut 62 2013 430 439
30. V.P. Singh, G.D. Bren, A. Algeciras-Schimnich Nelfinavir/ritonavir reduces acinar injury but not inflammation during mouse caerulein pancreatitis Am J Physiol Gastrointest Liver Physiol 296 2009 G1040 G1046
31. J. Mayerle, J. Schnekenburger, B. Kruger Extracellular cleavage of E-cadherin by leukocyte elastase during acute experimental pancreatitis in rats Gastroenterology 129 2005 1251 1267
32. T.M. Gress, F. Muller-Pillasch, M.M. Lerch Balance of expression of genes coding for extracellular matrix proteins and extracellular matrix degrading proteases in chronic pancreatitis Z Gastroenterol 32 1994 221 225
33. J.L. Van Laethem, P. Robberecht, A. Resibois Transforming growth factor beta promotes development of fibrosis after repeated courses of acute pancreatitis in mice Gastroenterology 110 1996 576 582
34. C. Guerra, A.J. Schuhmacher, M. Canamero Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice Cancer Cell 11 2007 291 302
35. J.P. Morris 4th, D.A. Cano, S. Sekine Beta-catenin blocks Kras-dependent reprogramming of acini into pancreatic cancer precursor lesions in mice J Clin Invest 120 2010 508 520
36. J.A. Williams, M. Korc, R.L. Dormer Action of secretagogues on a new preparation of functionally intact, isolated pancreatic acini Am J Physiol 235 1978 E517 E524
37. S.G. Voronina, S.L. Barrow, A.W. Simpson Dynamic changes in cytosolic and mitochondrial ATP levels in pancreatic acinar cells Gastroenterology 138 2010 1976 1987
38. S.D. Leach, I.M. Modlin, G.A. Scheele Intracellular activation of digestive zymogens in rat pancreatic acini Stimulation by high doses of cholecystokinin J Clin Invest 87 1991 362 366
39. T. Grady, M. Mah'moud, T. Otani Zymogen proteolysis within the pancreatic acinar cell is associated with cellular injury Am J Physiol 275 1998 G1010 G1017
40. B. Kruger, M.M. Lerch, W. Tessenow Direct detection of premature protease activation in living pancreatic acinar cells Lab Invest 78 1998 763 764
41. B. Kruger, E. Albrecht, M.M. Lerch The role of intracellular calcium signaling in premature protease activation and the onset of pancreatitis Am J Pathol 157 2000 43 50
42. J.B. Ward, O.H. Petersen, S.A. Jenkins Is an elevated concentration of acinar cytosolic free ionised calcium the trigger for acute pancreatitis? Lancet 346 1995 1016 1019
43. A.K. Saluja, L. Bhagat, H.S. Lee Secretagogue-induced digestive enzyme activation and cell injury in rat pancreatic acini Am J Physiol 276 1999 G835 G842
44. F. Mooren, V. Hlouschek, T. Finkes Early changes in pancreatic acinar cell calcium signaling after pancreatic duct obstruction J Biol Chem 278 2003 9361 9369
45. M.S. Kim, J.H. Hong, Q. Li Deletion of TRPC3 in mice reduces store-operated Ca2+ influx and the severity of acute pancreatitis Gastroenterology 137 2009 1509 1517
46. L. Zhang, K. Graziano, T. Pham Adenovirus-mediated gene transfer of dominant-negative Smad4 blocks TGF-beta signaling in pancreatic acinar cells Am J Physiol Gastrointest Liver Physiol 280 2001 G1247 G1253
47. N. Weng, M.D. Baumler, D.D. Thomas Functional role of J domain of cysteine string protein in Ca2+-dependent secretion from acinar cells Am J Physiol Gastrointest Liver Physiol 296 2009 G1030 G1039
48. N. Behrendorff, A. Shukla, C. Schwiening Local dynamic changes in confined extracellular environments within organs Clin Exp Pharmacol Physiol 36 2009 1010 1015
49. Y.C. Huang, M. Rupnik, H.Y. Gaisano Unperturbed islet alpha-cell function examined in mouse pancreas tissue slices J Physiol 589 2011 395 408
50. H. Volzke, S.E. Baumeister, D. Alte Independent risk factors for gallstone formation in a region with high cholelithiasis prevalence Digestion 71 2005 97 105
51. E.L. Opie The relation of cholelithiasis to disease of the pancreas and to fat-necrosis Johns Hopkins Hosp Bull 12 1901 19 21
52. E.L. Opie The etiology of acute hemorrhagic pancreatitis Johns Hopkins Hosp Bull 12 1901 182 188
53. C.A. Hernandez, M.M. Lerch Sphincter stenosis and gallstone migration through the biliary tract Lancet 341 1993 1371 1373
54. M.M. Lerch, C.A. Hernandez, G. Adler Acute pancreatitis N Engl J Med 331 1994 948 949
55. M. Lerch, A.K. Saluja, M. Runzi Pancreatic duct obstruction triggers acute necrotizing pancreatitis in the opossum Gastroenterology 104 1993 853 864
56. M.M. Lerch, H. Weidenbach, C.A. Hernandez Pancreatic outflow obstruction as the critical event for human gall stone induced pancreatitis Gut 35 1994 1501 1503
57. W. Halangk, M.M. Lerch, B. Brandt-Nedelev Role of cathepsin B in intracellular trypsinogen activation and the onset of acute pancreatitis J Clin Invest 106 2000 773 781
58. M.M. Lerch, A.K. Saluja, M. Runzi Luminal endocytosis and intracellular targeting by acinar cells during early biliary pancreatitis in the opossum J Clin Invest 95 1995 2222 2231
59. N.I. Walker, C.M. Winterford, J.F.R. Kerr Ultrastructure of the rat pancreas after experimental duct ligation II. Duct and stromal cell proliferation, differentiation, and deletion Pancreas 7 1993 420 434
60. G. Perides, J.M. Laukkarinen, G. Vassileva Biliary acute pancreatitis in mice is mediated by the G-protein-coupled cell surface bile acid receptor Gpbar1 Gastroenterology 138 2010 715 725
61. S. Voronina, R. Longbottom, R. Sutton Bile acids induce calcium signals in mouse pancreatic acinar cells: implications for bile-induced pancreatic pathology J Physiol 540 2002 49 55
62. S.Z. Husain, A.I. Orabi, K.A. Muili Ryanodine receptors contribute to bile acid-induced pathological calcium signaling and pancreatitis in mice Am J Physiol Gastrointest Liver Physiol 302 2012 G1423 G1433
63. D.M. Booth, J.A. Murphy, R. Mukherjee Reactive oxygen species induced by bile acid induce apoptosis and protect against necrosis in pancreatic acinar cells Gastroenterology 140 2011 2116 2125
64. M.M. Lerch, A.A. Aghdassi The role of bile acids in gallstone-induced pancreatitis Gastroenterology 138 2010 429 433
65. F.U. Weiss, P. Simon, N. Bogdanova Complete cystic fibrosis transmembrane conductance regulator gene sequencing in patients with idiopathic chronic pancreatitis and controls Gut 54 2005 1456 1460
66. M.J. Dimagno, S.H. Lee, Y. Hao A proinflammatory, antiapoptotic phenotype underlies the susceptibility to acute pancreatitis in cystic fibrosis transmembrane regulator (-/-) mice Gastroenterology 129 2005 665 681
67. P. Pallagi, V. Venglovecz, Z. Rakonczay Jr Trypsin reduces pancreatic ductal bicarbonate secretion by inhibiting CFTR Cl(-) channels and luminal anion exchangers Gastroenterology 141 2011 2228 2239.e6
68. M.D. Noble, J. Romac, S.R. Vigna A pH-sensitive, neurogenic pathway mediates disease severity in a model of post-ERCP pancreatitis Gut 57 2008 1566 1571
69. M.B. Fallon, F.S. Gorelick, J.M. Anderson Effect of caerulein hyperstimulation on the paracellular barrier of rat exocrine pancreas Gastroenterology 108 1995 1863 1872
70. T. Mizunuma, S. Kawamura, Y. Kishino Effects of injecting excess arginine on rat pancreas J Nutr 114 1984 467 471
71. S. Tani, H. Itoh, Y. Okabayashi New model of acute necrotizing pancreatitis induced by excessive doses of arginine in rats Dig Dis Sci 35 1990 367 374
72. C.P. Delaney, K.F. McGeeney, P. Dervan Pancreatic atrophy: a new model using serial intra-peritoneal injections of L-arginine Scand J Gastroenterol 28 1993 1086 1090
73. C. Weaver, A.E. Bishop, J.M. Polak Pancreatic changes elicited by chronic administration of excess L-arginine Exp Mol Pathol 60 1994 71 87
74. R. Sharif, R. Dawra, K. Wasiluk Impact of toll-like receptor 4 on the severity of acute pancreatitis and pancreatitis-associated lung injury in mice Gut 58 2009 813 819
75. Z. Rakonczay Jr, P. Hegyi, S. Dosa A new severe acute necrotizing pancreatitis model induced by L-ornithine in rats Crit Care Med 36 2008 2117 2127
76. G. Biczo, P. Hegyi, S. Dosa The crucial role of early mitochondrial injury in L-lysine-induced acute pancreatitis Antioxid Redox Signal 15 2011 2669 2681
77. W.H. Griffith, N.J. Wade The occurrence and prevention of hemorrhagic degeneration in young rats on a low choline diet J Biol Chem 131 1938 567 577
78. B. Lombardi, L. Ester, D. Longnecker Acute hemorrhage pancreatis (massive necrosis) with fat necrosis induced in mice by DL-ethionine fed with a choline deficit diet Am J Pathol 79 1975 465 480
79. K.N. Rao, P.K. Eagon, K. Okamura Acute hemorrhagic pancreatic necrosis in mice Induction in male mice treated with estradiol Am J Pathol 109 1982 8 14
80. S. Akita, K. Kubota, A. Kobayashi Role of bone marrow cells in the development of pancreatic fibrosis in a rat model of pancreatitis induced by a choline-deficient/ethionine-supplemented diet Biochem Biophys Res Commun 420 2012 743 749
81. L. Gilliland, M.L. Steer Effects of ethionine on digestive enzyme synthesis and discharge by mouse pancreas Am J Physiol 239 1980 G418 G426
82. U. Leli, A. Saluja, L. Picard Effects of a choline-deficient ethionine-supplemented diet on phospholipase C activity in mouse pancreatic acinar cell membranes and in electropermeabilized mouse pancreatic acini J Pharmacol Exp Ther 253 1990 847 850
83. S.D. Leach, A.J. Bilchik, O. Karapetian Influence of chloroquine on diet-induced pancreatitis Pancreas 8 1993 64 69
84. M.M. Lerch, H. Weidenbach, T.M. Gress Effect of kinin inhibition in experimental acute pancreatitis Am J Physiol 269 1995 G490 G499
85. A. Thal, E. Brackney Acute hemorrhagic pancreatic necrosis produced by local Shwartzman reaction: experimental study on pancreatitis JAMA 155 1954 569 574
86. D.T. Janigan, T.J. Nevalainen, M.A. MacAulay Foreign serum-induced pancreatitis in mice I. A new model of acute pancreatitis Lab Invest 33 1975 591 607
87. M. Tsuchitani, T. Saegusa, I. Narama A new diabetic strain of rat (WBN/Kob) Lab Anim 19 1985 200 207
88. S.V. Pakala, M.O. Kurrer, J.D. Katz T helper 2 (Th2) T cells induce acute pancreatitis and diabetes in immune-compromised nonobese diabetic (NOD) mice J Exp Med 186 1997 299 306
89. H. Kanno, M. Nose, J. Itoh Spontaneous development of pancreatitis in the MRL/Mp strain of mice in autoimmune mechanism Clin Exp Immunol 89 1992 68 73
90. W.M. Qu, T. Miyazaki, M. Terada A novel autoimmune pancreatitis model in MRL mice treated with polyinosinic:polycytidylic acid Clin Exp Immunol 129 2002 27 34
91. S.T. Chari, G. Kloeppel, L. Zhang Histopathologic and clinical subtypes of autoimmune pancreatitis: the honolulu consensus document Pancreatology 10 2010 664 672
92. T. Shimosegawa, S.T. Chari, L. Frulloni International consensus diagnostic criteria for autoimmune pancreatitis: guidelines of the International Association of Pancreatology Pancreas 40 2011 352 358
93. L.J. Murray, R. Lee, C. Martens In vivo cytokine gene expression in T cell subsets of the autoimmune MRL/Mp-lpr/lpr mouse Eur J Immunol 20 1990 163 170
94. A.A. Aghdassi, J. Mayerle, S. Christochowitz Animal models for investigating chronic pancreatitis Fibrogenesis Tissue Repair 4 2011 26
95. M. Yamasaki, Y. Takeyama, M. Shinkai Pancreatic and bile duct obstruction exacerbates rat caerulein-induced pancreatitis: a new experimental model of acute hemorrhagic pancreatitis J Gastroenterol 41 2006 352 360
96. I. Samuel, A. Chaudhary, R.A. Fisher Exacerbation of acute pancreatitis by combined cholinergic stimulation and duct obstruction Am J Surg 190 2005 721 724
97. T. Otani, A. Matsukura, T. Takamoto Effects of pancreatic duct ligation on pancreatic response to bombesin Am J Physiol Gastrointest Liver Physiol 290 2006 G633 G639
98. M. Miyauchi, K. Suda, C. Kuwayama Role of fibrosis-related genes and pancreatic duct obstruction in rat pancreatitis models: implications for chronic pancreatitis Histol Histopathol 22 2007 1119 1127
99. T. Tanaka, Y. Miura, Y. Matsugu Pancreatic duct obstruction is an aggravating factor in the canine model of chronic alcoholic pancreatitis Gastroenterology 115 1998 1248 1253
100. M. Yamamoto, M. Otani, M. Otsuki A new model of chronic pancreatitis in rats Am J Physiol Gastrointest Liver Physiol 291 2006 G700 G708
101. B.A. Neuschwander-Tetri, K.R. Bridle, L.D. Wells Repetitive acute pancreatic injury in the mouse induces procollagen alpha1(I) expression colocalized to pancreatic stellate cells Lab Invest 80 2000 143 150
102. T. Watanabe, A. Masamune, K. Kikuta Bone marrow contributes to the population of pancreatic stellate cells in mice Am J Physiol Gastrointest Liver Physiol 297 2009 G1138 G1146
103. M. Treiber, P. Neuhofer, E. Anetsberger Myeloid, but not pancreatic, RelA/p65 is required for fibrosis in a mouse model of chronic pancreatitis Gastroenterology 141 2011 1473 1485 1485.e1-7
104. A.L. Charrier, D.R. Brigstock Connective tissue growth factor production by activated pancreatic stellate cells in mouse alcoholic chronic pancreatitis Lab Invest 90 2010 1179 1188
105. A. Vonlaufen, Z. Xu, B. Daniel Bacterial endotoxin: a trigger factor for alcoholic pancreatitis? Evidence from a novel, physiologically relevant animal model Gastroenterology 133 2007 1293 1303
106. A. Vonlaufen, P.A. Phillips, Z. Xu Withdrawal of alcohol promotes regression while continued alcohol intake promotes persistence of LPS-induced pancreatic injury in alcohol-fed rats Gut 60 2011 238 246
107. G. Sparmann, J. Merkord, A. Jaschke Pancreatic fibrosis in experimental pancreatitis induced by dibutyltin dichloride Gastroenterology 112 1997 1664 1672
108. Q. Chen, L.P. Vera-Portocarrero, M.H. Ossipov Attenuation of persistent experimental pancreatitis pain by a bradykinin b2 receptor antagonist Pancreas 39 2010 1220 1225
109. M. Vardanyan, O.K. Melemedjian, T.J. Price Reversal of pancreatitis-induced pain by an orally available, small molecule interleukin-6 receptor antagonist Pain 151 2010 257 265
110. V. Puig-Divi, X. Molero, A. Salas Induction of chronic pancreatic disease by trinitrobenzene sulfonic acid infusion into rat pancreatic ducts Pancreas 13 1996 417 424
111. Y. Zhu, K. Mehta, C. Li Systemic administration of anti-NGF increases A-type potassium currents and decreases pancreatic nociceptor excitability in a rat model of chronic pancreatitis Am J Physiol Gastrointest Liver Physiol 302 2012 G176 G181
112. S. Ida, M. Ohmuraya, M. Hirota Chronic pancreatitis in mice by treatment with choline-deficient ethionine-supplemented diet Exp Anim 59 2010 421 429
113. D. Yadav, D.C. Whitcomb The role of alcohol and smoking in pancreatitis Nat Rev Gastroenterol Hepatol 7 2010 131 145
114. M. Alexandre, S.J. Pandol, F.S. Gorelick The emerging role of smoking in the development of pancreatitis Pancreatology 11 2011 469 474
115. U.A. Wittel, K.K. Pandey, M. Andrianifahanana Chronic pancreatic inflammation induced by environmental tobacco smoke inhalation in rats Am J Gastroenterol 101 2006 148 159
116. D.K. Meyerholz, D.A. Stoltz, A.A. Pezzulo Pathology of gastrointestinal organs in a porcine model of cystic fibrosis Am J Pathol 176 2010 1377 1389
117. M. Abu-El-Haija, S. Ramachandran, D.K. Meyerholz Pancreatic damage in fetal and newborn cystic fibrosis pigs involves the activation of inflammatory and remodeling pathways Am J Pathol 181 2012 499 507
118. F. Marrache, S.P. Tu, G. Bhagat Overexpression of interleukin-1beta in the murine pancreas results in chronic pancreatitis Gastroenterology 135 2008 1277 1287
119. B. Ji, L. Tsou, H. Wang Ras activity levels control the development of pancreatic diseases Gastroenterology 137 2009 1072 1082 1082.e1-6
120. J. Daniluk, Y. Liu, D. Deng An NF-kappaB pathway-mediated positive feedback loop amplifies Ras activity to pathological levels in mice J Clin Invest 122 2012 1519 1528
121. S.W. Park, J.M. Davison, J. Rhee Oncogenic KRAS induces progenitor cell expansion and malignant transformation in zebrafish exocrine pancreas Gastroenterology 134 2008 2080 2090
122. C. Gabbi, H.J. Kim, K. Hultenby Pancreatic exocrine insufficiency in LXRbeta-/- mice is associated with a reduction in aquaporin-1 expression Proc Natl Acad Sci U S A 105 2008 15052 15057
123. D.X. Feng, W. Peng, Y.F. Chen Down-regulation of aquaporin 1 in rats with experimental acute necrotizing pancreatitis Pancreas 41 2012 1092 1098
124. A. Iglesias, M. Murga, U. Laresgoiti Diabetes and exocrine pancreatic insufficiency in E2F1/E2F2 double-mutant mice J Clin Invest 113 2004 1398 1407
125. D.A. Cano, S. Sekine, M. Hebrok Primary cilia deletion in pancreatic epithelial cells results in cyst formation and pancreatitis Gastroenterology 131 2006 1856 1869
126. H.P. Harding, H. Zeng, Y. Zhang Diabetes mellitus and exocrine pancreatic dysfunction in perk-/- mice reveals a role for translational control in secretory cell survival Mol Cell 7 2001 1153 1163
127. K. Iida, Y. Li, B.C. McGrath PERK eIF2 alpha kinase is required to regulate the viability of the exocrine pancreas in mice BMC Cell Biol 8 2007 38
128. J.K. Colby, R.D. Klein, M.J. McArthur Progressive metaplastic and dysplastic changes in mouse pancreas induced by cyclooxygenase-2 overexpression Neoplasia 10 2008 782 796
129. T. Reding, U. Wagner, A.B. Silva Inflammation-dependent expression of SPARC during development of chronic pancreatitis in WBN/Kob rats and a microarray gene expression analysis Physiol Genomics 38 2009 196 204
130. H. Kayed, J. Kleeff, S. Keleg Distribution of Indian hedgehog and its receptors patched and smoothened in human chronic pancreatitis J Endocrinol 178 2003 467 478
131. M.S. Lee, D. Gu, L. Feng Accumulation of extracellular matrix and developmental dysregulation in the pancreas by transgenic production of transforming growth factor-beta 1 Am J Pathol 147 1995 42 52
132. R. Vogelmann, D. Ruf, M. Wagner Effects of fibrogenic mediators on the development of pancreatic fibrosis in a TGF-beta1 transgenic mouse model Am J Physiol Gastrointest Liver Physiol 280 2001 G164 G172
133. B. Baumann, M. Wagner, T. Aleksic Constitutive IKK2 activation in acinar cells is sufficient to induce pancreatitis in vivo J Clin Invest 117 2007 1502 1513
134. I.H. Jung, D.E. Jung, Y.N. Park Aberrant Hedgehog ligands induce progressive pancreatic fibrosis by paracrine activation of myofibroblasts and ductular cells in transgenic zebrafish PLoS One 6 2011 e27941
135. M.L. Casanova, A. Bravo, A. Ramirez Exocrine pancreatic disorders in transsgenic mice expressing human keratin 8 J Clin Invest 103 1999 1587 1595
136. N. Li, X. Wu, R.G. Holzer et al. Loss of acinar cell IKKα triggers spontaneous pancreatitis in mice J Clin Invest 2013 Apr 8 10.1172/JCI64498 [Epub ahead of print]
137. H. Archer, N. Jura, J. Keller A mouse model of hereditary pancreatitis generated by transgenic expression of R122H trypsinogen Gastroenterology 131 2006 1844 1855
138. L. Zhang, S. Chari, T.C. Smyrk Autoimmune pancreatitis (AIP) type 1 and type 2: an international consensus study on histopathologic diagnostic criteria Pancreas 40 2011 1172 1179
139. M. Yamashina, A. Nishio, S. Nakayama Comparative study on experimental autoimmune pancreatitis and its extrapancreatic involvement in mice Pancreas 41 2012 1255 1262
140. K. Uchida, K. Okazaki, T. Nishi Experimental immune-mediated pancreatitis in neonatally thymectomized mice immunized with carbonic anhydrase II and lactoferrin Lab Invest 82 2002 411 424
141. I. Haruta, K. Shimizu, N. Yanagisawa Commensal flora, is it an unwelcomed companion as a triggering factor of autoimmune pancreatitis? Front Physiol 3 2012 77
142. S.E. Ostrowski, A.A. Reilly, D.N. Collins Progression or resolution of coxsackievirus B4-induced pancreatitis: a genomic analysis J Virol 78 2004 8229 8237
143. M. Hindersson, A. Orn, R.A. Harris Strains of coxsackie virus B4 differed in their ability to induce acute pancreatitis and the responses were negatively correlated to glucose tolerance Arch Virol 149 2004 1985 2000
144. R. Gu, A. Shampang, A. Reilly IL-10 is pathogenic during the development of coxsackievirus B4-induced chronic pancreatitis Virology 395 2009 77 86
145. D.L. Clemens, T.R. Jerrells Ethanol consumption potentiates viral pancreatitis and may inhibit pancreas regeneration: preliminary findings Alcohol 33 2004 183 189
146. S. Navina, C. Acharya, J.P. DeLany Lipotoxicity causes multisystem organ failure and exacerbates acute pancreatitis in obesity Sci Transl Med 3 2011 107ra110
147. J.A. Sennello, R. Fayad, M. Pini Interleukin-18, together with interleukin-12, induces severe acute pancreatitis in obese but not in nonobese leptin-deficient mice Proc Natl Acad Sci U S A 105 2008 8085 8090