Animal models for studying epithelial barriers in neonatal necrotizing enterocolitis, inflammatory bowel disease and colorectal cancer

Tissue Barriers

Volumn 5, Issue 4, 2017, Pages

  Xing, Tiaosi ^a   Camacho Salazar, Rolando ^a   Chen, Yan Hua ^a  

^a EAST CAROLINA UNIVERSITY   (United States)

Author keywords

claudins; colorectal cancer; epithelial barriers; inflammatory bowel disease; necrotizing enterocolitis; tight junctions

Indexed keywords

CLAUDIN; CLAUDIN 2; CLAUDIN 3; CLAUDIN 7; EPITHELIAL CELL ADHESION MOLECULE; JUNCTIONAL ADHESION MOLECULE; JUNCTIONAL ADHESION MOLECULE A; JUNCTIONAL ADHESION MOLECULE B; JUNCTIONAL ADHESION MOLECULE C; OCCLUDIN; TRICELLULIN;

CARCINOGENESIS; CELL ADHESION; CELL GROWTH; CELL PROLIFERATION; COLORECTAL CANCER; CROHN DISEASE; DYSBIOSIS; ENTERITIS; GENE EXPRESSION; HUMAN; INFLAMMATORY BOWEL DISEASE; INTESTINE EPITHELIUM; MEMBRANE DAMAGE; NECROTIZING ENTEROCOLITIS; NONHUMAN; PATHOPHYSIOLOGY; PIGLET; PROTEIN EXPRESSION; REVIEW; RODENT; SIGNAL TRANSDUCTION; TIGHT JUNCTION; ULCERATIVE COLITIS; ANIMAL; COLORECTAL TUMOR; DISEASE MODEL; EPITHELIUM; GENE KNOCK-IN; GENETICS; KNOCKOUT MOUSE; METABOLISM; MOUSE; NEWBORN; PATHOLOGY; PIG; PROCEDURES; RAT;

ANIMALS; COLORECTAL NEOPLASMS; DISEASE MODELS, ANIMAL; ENTEROCOLITIS, NECROTIZING; EPITHELIUM; GENE KNOCK-IN TECHNIQUES; HUMANS; INFANT, NEWBORN; INFLAMMATORY BOWEL DISEASES; MICE; MICE, KNOCKOUT; RATS; SWINE;

EID: 85027115930     PISSN: 21688362     EISSN: 21688370     Source Type: Journal    
DOI: 10.1080/21688370.2017.1356901     Document Type: Review

References (147)

1. Lee SH. Intestinal permeability regulation by tight junction: Implication on Inflamm Bowel Dis. Intest Res. 2015; 13:11-8. https://doi.org/10.5217/ir.2015.13.1.11. PMID:25691839
2. Shen L, Su L, Turner JR. Mechanisms and functional implications of intestinal barrier defects. Dig Dis. 2009; 27:443-9. https://doi.org/10.1159/000233282. PMID:19897958
3. Ciccocioppo R, Finamore A, Ara C, Di Sabatino A, Mengheri E, Corazza GR. Altered expression, localization, and phosphorylation of epithelial junctional proteins in celiac disease. Am J Clin Pathol. 2006; 125:502-11. https://doi.org/10.1309/DTYRA91G8R0KTM8M. PMID:16627260
4. Das P, Goswami P, Das TK, Nag T, Sreenivas V, Ahuja V, Panda SK, Gupta SD, Makharia GK. Comparative tight junction protein expressions in colonic Crohn's disease, ulcerative colitis, and tuberculosis: A new perspective. Virchows Arch. 2012; 460:261-70. https://doi.org/10.1007/s00428-012-1195-1. PMID:22297703
5. Suzuki T, Yoshinaga N, Tanabe S. Interleukin-6 (IL-6) regulates claudin-2 expression and tight junction permeability in intestinal epithelium. J Biol Chem. 2011; 286:31263-71. https://doi.org/10.1074/jbc.M111.238147. PMID:21771795
6. Furuse M, Hirase T, Itoh M, Nagafuchi A, Yonemura S, Tsukita S, Tsukita S. Occludin: A novel integral membrane protein localizing at tight junctions. J Cell Biol. 1993; 123:1777-88. https://doi.org/10.1083/jcb.123.6.1777. PMID:8276896
7. Gunzel D, Yu AS. Claudins and the modulation of tight junction permeability. Physiol Rev. 2013; 93:525-69. https://doi.org/10.1152/physrev.00019.2012. PMID:23589827
8. Lu Z, Ding L, Lu Q, Chen YH. Claudins in intestines: Distribution and functional significance in health and diseases. Tissue Barriers. 2013; 1:e24978. https://doi.org/10.4161/tisb.24978. PMID:24478939
9. Pope JL, Bhat AA, Sharma A, Ahmad R, Krishnan M, Washington MK, Beauchamp RD, Singh AB, Dhawan P. Claudin-1 regulates intestinal epithelial homeostasis through the modulation of Notch-signalling. Gut. 2014; 63:622-34. https://doi.org/10.1136/gutjnl-2012-304241
10. Nishida M, Yoshida M, Nishiumi S, Furuse M, Azuma T. Claudin-2 regulates colorectal inflammation via myosin light chain kinase-dependent signaling. Dig Dis Sci. 2013; 58:1546-59. https://doi.org/10.1007/s10620-012-2535-3
11. Ding L, Lu Z, Foreman O, Tatum R, Lu Q, Renegar R, Cao J, Chen YH. Inflammation and disruption of the mucosal architecture in claudin-7-deficient mice. Gastroenterology. 2012; 142:305-15. https://doi.org/10.1053/j.gastro.2011.10.025. PMID:22044670
12. Tamura A, Kitano Y, Hata M, Katsuno T, Moriwaki K, Sasaki H, Hayashi H, Suzuki Y, Noda T, Furuse M, et al. Megaintestine in claudin-15-deficient mice. Gastroenterology. 2008; 134:523-34. https://doi.org/10.1053/j.gastro.2007.11.040. PMID:18242218
13. Lei Z, Maeda T, Tamura A, Nakamura T, Yamazaki Y, Shiratori H, Yashiro K, Tsukita S, Hamada H. EpCAM contributes to formation of functional tight junction in the intestinal epithelium by recruiting claudin proteins. Dev Biol. 2012; 371:136-45. https://doi.org/10.1016/j.ydbio.2012.07.005. PMID:22819673
14. Furuse M, Itoh M, Hirase T, Nagafuchi A, Yonemura S, Tsukita S, Tsukita S. Direct association of occludin with ZO-1 and its possible involvement in the localization of occludin at tight junctions. J Cell Biol. 1994; 127:1617-26. https://doi.org/10.1083/jcb.127.6.1617
15. Yu AS, McCarthy KM, Francis SA, McCormack JM, Lai J, Rogers RA, Lynch RD, Schneeberger EE. Knockdown of occludin expression leads to diverse phenotypic alterations in epithelial cells. Am J Physiol Cell Physiol. 2005; 288:C1231-41. https://doi.org/10.1152/ajpcell.00581.2004. PMID:15689410
16. Saitou M, Furuse M, Sasaki H, Schulzke JD, Fromm M, Takano H, Noda T, Tsukita S. Complex phenotype of mice lacking occludin, a component of tight junction strands. Mol Biol Cell. 2000; 11:4131-42. https://doi.org/10.1091/mbc.11.12.4131
17. Schulzke JD, Gitter AH, Mankertz J, Spiegel S, Seidler U, Amasheh S, Saitou M, Tsukita S, Fromm M. Epithelial transport and barrier function in occludin-deficient mice. Biochim Biophys Acta. 2005; 1669:34-42. https://doi.org/10.1016/j.bbamem.2005.01.008. PMID:15842997
18. Mir H, Meena AS, Chaudhry KK, Shukla PK, Gangwar R, Manda B, Padala MK, Shen L, Turner JR, Dietrich P, et al. Occludin deficiency promotes ethanol-induced disruption of colonic epithelial junctions, gut barrier dysfunction and liver damage in mice. Biochim Biophys Acta. 2016; 1860:765-74. https://doi.org/10.1016/j.bbagen.2015.12.013. PMID:26721332
19. Coeffier M, Gloro R, Boukhettala N, Aziz M, Lecleire S, Vandaele N, Antonietti M, Savoye G, Bôle-Feysot C, Déchelotte P, et al. Increased proteasome-mediated degradation of occludin in irritable bowel syndrome. Am J Gastroenterol. 2010; 105:1181-8. https://doi.org/10.1038/ajg.2009.700. PMID:19997094
20. Martin-Padura I, Lostaglio S, Schneemann M, Williams L, Romano M, Fruscella P, Panzeri C, Stoppacciaro A, Ruco L, Villa A, et al. Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration. J Cell Biol. 1998; 142:117-27. https://doi.org/10.1083/jcb.142.1.117
21. Jia W, Martin TA, Zhang G, Jiang WG. Junctional adhesion molecules in cerebral endothelial tight junction and brain metastasis. Anticancer Res. 2013; 33:2353-9. PMID:23749882
22. Aurrand-Lions M, Duncan L, Ballestrem C, Imhof BA. JAM-2, a novel immunoglobulin superfamily molecule, expressed by endothelial and lymphatic cells. J Biol Chem 2001; 276:2733-41. https://doi.org/10.1074/jbc.M005458200. PMID:11053409
23. Santoso S, Sachs UJ, Kroll H, Linder M, Ruf A, Preissner KT, Chavakis T. The junctional adhesion molecule 3 (JAM-3) on human platelets is a counterreceptor for the leukocyte integrin Mac-1. J Exp Med. 2002; 196:679-91. https://doi.org/10.1084/jem.20020267
24. Hirabayashi S, Tajima M, Yao I, Nishimura W, Mori H, Hata Y. JAM4, a junctional cell adhesion molecule interacting with a tight junction protein, MAGI-1. Mol Cell Biol. 2003; 23:4267-82. https://doi.org/10.1128/MCB.23.12.4267-4282.2003
25. Bazzoni G, Martinez-Estrada OM, Orsenigo F, Cordenonsi M, Citi S, Dejana E. Interaction of junctional adhesion molecule with the tight junction components ZO-1, cingulin, and occludin. J Biol Chem. 2000; 275:20520-6. https://doi.org/10.1074/jbc.M905251199
26. Johnson-Leger CA, Aurrand-Lions M, Beltraminelli N, Fasel N, Imhof BA. Junctional adhesion molecule-2 (JAM-2) promotes lymphocyte transendothelial migration. Blood. 2002; 100:2479-86. https://doi.org/10.1182/blood-2001-11-0098
27. Mandell KJ, Babbin BA, Nusrat A, Parkos CA. Junctional adhesion molecule 1 regulates epithelial cell morphology through effects on beta1 integrins and Rap1 activity. J Biol Chem. 2005; 280:11665-74. https://doi.org/10.1074/jbc.M412650200
28. Laukoetter MG, Nava P, Lee WY, Severson EA, Capaldo CT, Babbin BA, Williams IR, Koval M, Peatman E, Campbell JA, et al. JAM-A regulates permeability and inflammation in the intestine in vivo. J Exp Med. 2007; 204:3067-76. https://doi.org/10.1084/jem.20071416
29. Vetrano S, Rescigno M, Cera MR, Correale C, Rumio C, Doni A, Fantini M, Sturm A, Borroni E, Repici A, et al. Unique role of junctional adhesion molecule-a in maintaining mucosal homeostasis in inflammatory bowel disease. Gastroenterology. 2008; 135:173-84. https://doi.org/10.1053/j.gastro.2008.04.002
30. Vetrano S, Danese S. The role of JAM-A in inflammatory bowel disease: Unrevealing the ties that bind. Ann N Y Acad Sci. 2009; 1165:308-13. https://doi.org/10.1111/j.1749-6632.2009.04045.x. PMID:19538321
31. Wilcz-Villega EM, McClean S, O'Sullivan MA. Mast cell tryptase reduces junctional adhesion molecule-A (JAM-A) expression in intestinal epithelial cells: Implications for the mechanisms of barrier dysfunction in irritable bowel syndrome. Am J Gastroenterol. 2013; 108:1140-51. https://doi.org/10.1038/ajg.2013.92. PMID:23588236
32. Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S. Claudin-1 and −2: Novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol. 1998; 141:1539-50. https://doi.org/10.1083/jcb.141.7.1539
33. Furuse M, Hata M, Furuse K, Yoshida Y, Haratake A, Sugitani Y, Noda T, Kubo A, Tsukita S. Claudin-based tight junctions are crucial for the mammalian epidermal barrier: A lesson from claudin-1-deficient mice. J Cell Biol. 2002; 156:1099-111. https://doi.org/10.1083/jcb.200110122
34. Pope JL, Ahmad R, Bhat AA, Washington MK, Singh AB, Dhawan P. Claudin-1 overexpression in intestinal epithelial cells enhances susceptibility to adenamatous polyposis coli-mediated colon tumorigenesis. Mol Cancer. 2014; 13:167. https://doi.org/10.1186/1476-4598-13-167
35. Karabulut M, Alis H, Bas K, Karabulut S, Afsar CU, Oguz H, Gunaldi M, Akarsu C, Kones O, Aykan NF. Clinical significance of serum claudin-1 and claudin-7 levels in patients with colorectal cancer. Mol Clin Oncol. 2015; 3:1255-67
36. Nakagawa S, Miyoshi N, Ishii H, Mimori K, Tanaka F, Sekimoto M, Doki Y, Mori M. Expression of CLDN1 in colorectal cancer: A novel marker for prognosis. Int J Oncol. 2011; 39:791-6
37. Miwa N, Furuse M, Tsukita S, Niikawa N, Nakamura Y, Furukawa Y. Involvement of claudin-1 in the beta-catenin/Tcf signaling pathway and its frequent upregulation in human colorectal cancers. Oncol Res. 2001; 12:469-76. https://doi.org/10.3727/096504001108747477
38. Bhat AA, Ahmad R, Uppada SB, Singh AB, Dhawan P. Claudin-1 promotes TNF-alpha-induced epithelial-mesenchymal transition and migration in colorectal adenocarcinoma cells. Exp Cell Res. 2016; 349:119-27. https://doi.org/10.1016/j.yexcr.2016.10.005
39. Singh AB, Sharma A, Dhawan P. Claudin-1 expression confers resistance to anoikis in colon cancer cells in a Src-dependent manner. Carcinogenesis. 2012; 33:2538-47. https://doi.org/10.1093/carcin/bgs275
40. Furuse M, Furuse K, Sasaki H, Tsukita S. Conversion of zonulae occludentes from tight to leaky strand type by introducing claudin-2 into Madin-Darby canine kidney I cells. J Cell Biol. 2001; 153:263-72. https://doi.org/10.1083/jcb.153.2.263
41. Fujita H, Sugimoto K, Inatomi S, Maeda T, Osanai M, Uchiyama Y, Yamamoto Y, Wada T, Kojima T, Yokozaki H, et al. Tight junction proteins claudin-2 and −12 are critical for vitamin D-dependent Ca2+ absorption between enterocytes. Mol Biol Cell. 2008; 19:1912-21. https://doi.org/10.1091/mbc.E07-09-0973
42. Rosenthal R, Milatz S, Krug SM, Oelrich B, Schulzke JD, Amasheh S, Günzel D, Fromm M. Claudin-2, a component of the tight junction, forms a paracellular water channel. J Cell Sci. 2010; 123:1913-21. https://doi.org/10.1242/jcs.060665
43. Aung PP, Mitani Y, Sanada Y, Nakayama H, Matsusaki K, Yasui W. Differential expression of claudin-2 in normal human tissues and gastrointestinal carcinomas. Virchows Arch. 2006; 448:428-34. https://doi.org/10.1007/s00428-005-0120-2
44. Tamura A, Hayashi H, Imasato M, Yamazaki Y, Hagiwara A, Wada M, Noda T, Watanabe M, Suzuki Y, Tsukita S. Loss of claudin-15, but not claudin-2, causes Na+ deficiency and glucose malabsorption in mouse small intestine. Gastroenterology. 2011; 140:913-23. https://doi.org/10.1053/j.gastro.2010.08.006
45. Luettig J, Rosenthal R, Barmeyer C, Schulzke JD. Claudin-2 as a mediator of leaky gut barrier during intestinal inflammation. Tissue Barriers. 2015; 3:e977176. https://doi.org/10.4161/21688370.2014.977176
46. Ahmad R, Chaturvedi R, Olivares-Villagomez D, Habib T, Asim M, Shivesh P, Polk DB, Wilson KT, Washington MK, Van Kaer L, et al. Targeted colonic claudin-2 expression renders resistance to epithelial injury, induces immune suppression, and protects from colitis. Mucosal Immunol. 2014; 7:1340-53. https://doi.org/10.1038/mi.2014.21
47. Fujita H, Chiba H, Yokozaki H, Sakai N, Sugimoto K, Wada T, Kojima T, Yamashita T, Sawada N. Differential expression and subcellular localization of claudin-7, −8, −12, −13, and −15 along the mouse intestine. J Histochem Cytochem. 2006; 54:933-44. https://doi.org/10.1369/jhc.6A6944.2006. PMID:16651389
48. Tanaka H, Takechi M, Kiyonari H, Shioi G, Tamura A, Tsukita S. Intestinal deletion of Claudin-7 enhances paracellular organic solute flux and initiates colonic inflammation in mice. Gut. 2015; 64:1529-38. https://doi.org/10.1136/gutjnl-2014-308419
49. Wongdee K, Teerapornpuntakit J, Siangpro C, Chaipai S, Charoenphandhu N. Duodenal villous hypertrophy and upregulation of claudin-15 protein expression in lactating rats. J Mol Histol. 2013; 44:103-9. https://doi.org/10.1007/s10735-012-9451-x
50. Wada M, Tamura A, Takahashi N, Tsukita S. Loss of claudins 2 and 15 from mice causes defects in paracellular Na+ flow and nutrient transport in gut and leads to death from malnutrition. Gastroenterology. 2013; 144:369-80. https://doi.org/10.1053/j.gastro.2012.10.035
51. Trzpis M, McLaughlin PM, de Leij LM, Harmsen MC. Epithelial cell adhesion molecule: More than a carcinoma marker and adhesion molecule. Am J Pathol. 2007; 171:386-95. https://doi.org/10.2353/ajpath.2007.070152
52. Schnell U, Cirulli V, Giepmans BN. EpCAM: Structure and function in health and disease. Biochim Biophys Acta. 2013; 1828:1989-2001. https://doi.org/10.1016/j.bbamem.2013.04.018
53. Baeuerle PA, Gires O. EpCAM (CD326) finding its role in cancer. Br J Cancer 2007; 96:417-23. https://doi.org/10.1038/sj.bjc.6603494
54. Sivagnanam M, Mueller JL, Lee H, Chen Z, Nelson SF, Turner D, Zlotkin SH, Pencharz PB, Ngan BY, Libiger O, et al. Identification of EpCAM as the gene for congenital tufting enteropathy. Gastroenterology. 2008; 135:429-37. https://doi.org/10.1053/j.gastro.2008.05.036
55. Mueller JL, McGeough MD, Pena CA, Sivagnanam M. Functional consequences of EpCam mutation in mice and men. Am J Physiol Gastrointest Liver Physiol. 2014; 306:G278-88. https://doi.org/10.1152/ajpgi.00286.2013
56. Guerra E, Lattanzio R, La Sorda R, Dini F, Tiboni GM, Piantelli M, Alberti S. mTrop1/Epcam knockout mice develop congenital tufting enteropathy through dysregulation of intestinal E-cadherin/beta-catenin. PloS One. 2012; 7:e49302. https://doi.org/10.1371/journal.pone.0049302
57. Walsh MC, Kliegman RM. Necrotizing enterocolitis: Treatment based on staging criteria. Pediatr Clin North Am. 1986; 33:179-201. https://doi.org/10.1016/S0031-3955(16)34975-6
58. Ballance WA, Dahms BB, Shenker N, Kliegman RM. Pathology of neonatal necrotizing enterocolitis: A ten-year experience. J Pediatr. 1990; 117:S6-13. https://doi.org/10.1016/S0022-3476(05)81124-2
59. Emami CN, Petrosyan M, Giuliani S, Williams M, Hunter C, Prasadarao NV, Ford HR. Role of the host defense system and intestinal microbial flora in the pathogenesis of necrotizing enterocolitis. Surg Infect. 2009; 10:407-17. https://doi.org/10.1089/sur.2009.054
60. Lu P, Sodhi CP, Jia H, Shaffiey S, Good M, Branca MF, Hackam DJ. Animal models of gastrointestinal and liver diseases. Animal models of necrotizing enterocolitis: Pathophysiology, translational relevance, and challenges. Am J Physiol Gastrointest Liver Physiol. 2014; 306:G917-28. https://doi.org/10.1152/ajpgi.00422.2013
61. Barlow B, Santulli TV. Importance of multiple episodes of hypoxia or cold stress on the development of enterocolitis in an animal model. Surgery. 1975; 77:687-90
62. Caplan MS, Hedlund E, Adler L, Hsueh W. Role of asphyxia and feeding in a neonatal rat model of necrotizing enterocolitis. Pediatr Pathol. 1994; 14:1017-28. https://doi.org/10.3109/15513819409037698
63. Nadler EP, Dickinson E, Knisely A, Zhang XR, Boyle P, Beer-Stolz D, Watkins SC, Ford HR. Expression of inducible nitric oxide synthase and interleukin-12 in experimental necrotizing enterocolitis. J Surg Res. 2000; 92:71-7. https://doi.org/10.1006/jsre.2000.5877
64. Jilling T, Simon D, Lu J, Meng FJ, Li D, Schy R, Thomson RB, Soliman A, Arditi M, Caplan MS. The roles of bacteria and TLR4 in rat and murine models of necrotizing enterocolitis. J Immunol. 2006; 177:3273-82. https://doi.org/10.4049/jimmunol.177.5.3273
65. Guner YS, Franklin AL, Chokshi NK, Castle SL, Pontarelli E, Wang J, Wang L, Prasadarao NV, Upperman JS, Grishin AV, et al. P-glycoprotein induction by breast milk attenuates intestinal inflammation in experimental necrotizing enterocolitis. Lab Invest. 2011; 91:1668-79. https://doi.org/10.1038/labinvest.2011.113
66. Leaphart CL, Qureshi F, Cetin S, Li J, Dubowski T, Baty C, Beer-Stolz D, Guo F, Murray SA, Hackam DJ. Interferon-gamma inhibits intestinal restitution by preventing gap junction communication between enterocytes. Gastroenterology. 2007; 132:2395-411. https://doi.org/10.1053/j.gastro.2007.03.029
67. Garg PM, Tatum R, Ravisankar S, Shekhawat PS, Chen YH. Necrotizing enterocolitis in a mouse model leads to widespread renal inflammation, acute kidney injury, and disruption of renal tight junction proteins. Pediatr Res. 2015; 78:527-32. https://doi.org/10.1038/pr.2015.146
68. Oosterloo BC, Premkumar M, Stoll B, Olutoye O, Thymann T, Sangild PT, Burrin DG. Dual purpose use of preterm piglets as a model of pediatric GI disease. Vet Immunol Immunopathol. 2014; 159:156-65. https://doi.org/10.1016/j.vetimm.2014.02.012
69. Sibbons P, Spitz L, van Velzen D, Bullock GR. Relationship of birth weight to the pathogenesis of necrotizing enterocolitis in the neonatal piglet. Pediatr Pathol. 1988; 8:151-62. https://doi.org/10.3109/15513818809022292
70. Cohen IT, Nelson SD, Moxley RA, Hirsh MP, Counihan TC, Martin RF. Necrotizing enterocolitis in a neonatal piglet model. J Pediatr Surg. 1991; 26:598-601. https://doi.org/10.1016/0022-3468(91)90716-7
71. Sangild PT, Petersen YM, Schmidt M, Elnif J, Petersen TK, Buddington RK, Greisen G, Michaelsen KF, Burrin DG. Preterm birth affects the intestinal response to parenteral and enteral nutrition in newborn pigs. J Nutr. 2002; 132:3786-94
72. Sodhi C, Richardson W, Gribar S, Hackam DJ. The development of animal models for the study of necrotizing enterocolitis. Dis Models Mech. 2008; 1:94-8. https://doi.org/10.1242/dmm.000315
73. Halpern MD, Denning PW. The role of intestinal epithelial barrier function in the development of NEC. Tissue Barriers. 2015; 3:e1000707. https://doi.org/10.1080/21688370.2014.1000707
74. Rentea RM, Liedel JL, Welak SR, Cassidy LD, Mayer AN, Pritchard KA, Jr., Oldham KT, Gourlay DM. Intestinal alkaline phosphatase administration in newborns is protective of gut barrier function in a neonatal necrotizing enterocolitis rat model. J Pediatr Surg. 2012; 47:1135-42. https://doi.org/10.1016/j.jpedsurg.2012.03.018
75. Shiou SR, Yu Y, Chen S, Ciancio MJ, Petrof EO, Sun J, Claud EC. Erythropoietin protects intestinal epithelial barrier function and lowers the incidence of experimental neonatal necrotizing enterocolitis. J Biol Chem. 2011; 286:12123-32. https://doi.org/10.1074/jbc.M110.154625
76. Hogberg N, Stenback A, Carlsson PO, Wanders A, Lilja HE. Genes regulating tight junctions and cell adhesion are altered in early experimental necrotizing enterocolitis. J Pediatr Surg 2013; 48:2308-12. https://doi.org/10.1016/j.jpedsurg.2013.06.027
77. Clark JA, Doelle SM, Halpern MD, Saunders TA, Holubec H, Dvorak K, Boitano SA, Dvorak B. Intestinal barrier failure during experimental necrotizing enterocolitis: Protective effect of EGF treatment. Am J Physiol Gastrointest Liver Physiol. 2006; 291:G938-49. https://doi.org/10.1152/ajpgi.00090.2006
78. Ling X, Linglong P, Weixia D, Hong W. Protective Effects of Bifidobacterium on Intestinal Barrier Function in LPS-Induced Enterocyte Barrier Injury of Caco-2 Monolayers and in a Rat NEC Model. PloS One. 2016; 11:e0161635. https://doi.org/10.1371/journal.pone.0161635
79. Hunter CJ, Upperman JS, Ford HR, Camerini V. Understanding the susceptibility of the premature infant to necrotizing enterocolitis (NEC). Pediatr Res. 2008; 63:117-23. https://doi.org/10.1203/PDR.0b013e31815ed64c
80. Bergmann KR, Liu SX, Tian R, Kushnir A, Turner JR, Li HL, Chou PM, Weber CR, De Plaen IG. Bifidobacteria stabilize claudins at tight junctions and prevent intestinal barrier dysfunction in mouse necrotizing enterocolitis. Am J Pathol. 2013; 182:1595-606. https://doi.org/10.1016/j.ajpath.2013.01.013
81. Boivin MA, Ye D, Kennedy JC, Al-Sadi R, Shepela C, Ma TY. Mechanism of glucocorticoid regulation of the intestinal tight junction barrier. Am J Physiol Gastrointest Liver Physiol. 2007; 292:G590-8. https://doi.org/10.1152/ajpgi.00252.2006
82. Clayburgh DR, Rosen S, Witkowski ED, Wang F, Blair S, Dudek S, Garcia JG, Alverdy JC, Turner JR. A differentiation-dependent splice variant of myosin light chain kinase, MLCK1, regulates epithelial tight junction permeability. J Biol Chem. 2004; 279:55506-13. https://doi.org/10.1074/jbc.M408822200
83. Han X, Fink MP, Delude RL. Proinflammatory cytokines cause NO*-dependent and -independent changes in expression and localization of tight junction proteins in intestinal epithelial cells. Shock. 2003; 19:229-37. https://doi.org/10.1097/00024382-200303000-00006
84. Arrieta MC, Bistritz L, Meddings JB. Alterations in intestinal permeability. Gut. 2006; 55:1512-20. https://doi.org/10.1136/gut.2005.085373
85. Heiskala M, Peterson PA, Yang Y. The roles of claudin superfamily proteins in paracellular transport. Traffic. 2001; 2:93-8. https://doi.org/10.1034/j.1600-0854.2001.020203.x
86. Antoni L, Nuding S, Wehkamp J, Stange EF. Intestinal barrier in inflammatory bowel disease. World J Gastroenterol. 2014; 20:1165-79. https://doi.org/10.3748/wjg.v20.i5.1165
87. Oshitani N, Watanabe K, Nakamura S, Fujiwara Y, Higuchi K, Arakawa T. Dislocation of tight junction proteins without F-actin disruption in inactive Crohn's disease. Int J Mol Med. 2005; 15:407-10
88. Zeissig S, Burgel N, Gunzel D, Richter J, Mankertz J, Wahnschaffe U, Kroesen AJ, Zeitz M, Fromm M, Schulzke JD. Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease. Gut. 2007; 56:61-72. https://doi.org/10.1136/gut.2006.094375
89. Yamamoto-Furusho JK, Mendivil EJ, Fonseca-Camarillo G. Differential expression of occludin in patients with ulcerative colitis and healthy controls. Inflamm Bowel Dis. 2012; 18:E1999. https://doi.org/10.1002/ibd.22835
90. Prasad S, Mingrino R, Kaukinen K, Hayes KL, Powell RM, MacDonald TT, Collins JE. Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells. Lab Invest. 2005; 85:1139-62. https://doi.org/10.1038/labinvest.3700316
91. Weber CR, Nalle SC, Tretiakova M, Rubin DT, Turner JR. Claudin-1 and claudin-2 expression is elevated in inflammatory bowel disease and may contribute to early neoplastic transformation. Lab Invest. 2008; 88:1110-20. https://doi.org/10.1038/labinvest.2008.78
92. Mees ST, Mennigen R, Spieker T, Rijcken E, Senninger N, Haier J, Bruewer M. Expression of tight and adherens junction proteins in ulcerative colitis associated colorectal carcinoma: Upregulation of claudin-1, claudin-3, claudin-4, and beta-catenin. Int J Colorectal Dis. 2009; 24:361-8. https://doi.org/10.1007/s00384-009-0653-y
93. Stio M, Retico L, Annese V, Bonanomi AG. Vitamin D regulates the tight-junction protein expression in active ulcerative colitis. Scand J Gastroenterol. 2016; 51:1-7
94. Zwiers A, Fuss IJ, Leijen S, Mulder CJ, Kraal G, Bouma G. Increased expression of the tight junction molecule claudin-18 A1 in both experimental colitis and ulcerative colitis. Inflamm Bowel Dis. 2008; 14:1652-9. https://doi.org/10.1002/ibd.20695
95. Jiminez JA, Uwiera TC, Douglas Inglis G, Uwiera RR. Animal models to study acute and chronic intestinal inflammation in mammals. Gut Pathog. 2015; 7:29. https://doi.org/10.1186/s13099-015-0076-y
96. Bailey RW, Bourne EJ. Intracellular glycosidases of dextran-producing bacteria. Nature. 1961; 191:277-8. https://doi.org/10.1038/191277a0
97. Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology. 1990; 98:694-702. https://doi.org/10.1016/0016-5085(90)90290-H
98. Cooper HS, Murthy SN, Shah RS, Sedergran DJ. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest. 1993; 69:238-49
99. Lund PK, Zuniga CC. Intestinal fibrosis in human and experimental inflammatory bowel disease. Curr Opin Gastroenterol. 2001; 17:318-23. https://doi.org/10.1097/00001574-200107000-00004
100. Poritz LS, Garver KI, Green C, Fitzpatrick L, Ruggiero F, Koltun WA. Loss of the tight junction protein ZO-1 in dextran sulfate sodium induced colitis. J Surg Res. 2007; 140:12-9. https://doi.org/10.1016/j.jss.2006.07.050
101. Li X, Wang Q, Xu H, Tao L, Lu J, Cai L, Wang C. Somatostatin regulates tight junction proteins expression in colitis mice. Int J Clin Exp Pathol. 2014; 7:2153-62
102. De Salvo C, Ray S, Pizarro TT. Mechanisms and models for intestinal fibrosis in IBD. Dig Dis. 2014; 32(Suppl 1):26-34. https://doi.org/10.1159/000367822
103. Antoniou E, Margonis GA, Angelou A, Pikouli A, Argiri P, Karavokyros I, Papalois A, Pikoulis E. The TNBS-induced colitis animal model: An overview. Ann Med Surg. 2016; 11:9-15. https://doi.org/10.1016/j.amsu.2016.07.019
104. Gerlach K, McKenzie AN, Neurath MF, Weigmann B. IL-9 regulates intestinal barrier function in experimental T cell-mediated colitis. Tissue Barriers. 2015; 3:e983777. https://doi.org/10.4161/21688370.2014.983777
105. Han X, Ren X, Jurickova I, Groschwitz K, Pasternak BA, Xu H, Wilson TA, Hogan SP, Denson LA. Regulation of intestinal barrier function by signal transducer and activator of transcription 5b. Gut. 2009; 58:49-58. https://doi.org/10.1136/gut.2007.145094
106. Sun X, Yang H, Nose K, Nose S, Haxhija EQ, Koga H, Feng Y, Teitelbaum DH. Decline in intestinal mucosal IL-10 expression and decreased intestinal barrier function in a mouse model of total parenteral nutrition. Am J Physiol Gastrointest Liver Physiol. 2008; 294:G139-47. https://doi.org/10.1152/ajpgi.00386.2007
107. Madsen KL, Malfair D, Gray D, Doyle JS, Jewell LD, Fedorak RN. Interleukin-10 gene-deficient mice develop a primary intestinal permeability defect in response to enteric microflora. Inflamm Bowel Dis. 1999; 5:262-70. https://doi.org/10.1097/00054725-199911000-00004
108. Pizarro TT, Pastorelli L, Bamias G, Garg RR, Reuter BK, Mercado JR, Chieppa M, Arseneau KO, Ley K, Cominelli F. SAMP1/YitFc mouse strain: A spontaneous model of Crohn's disease-like ileitis. Inflamm Bowel Dis. 2011; 17:2566-84. https://doi.org/10.1002/ibd.21638
109. Olson TS, Reuter BK, Scott KG, Morris MA, Wang XM, Hancock LN, Burcin TL, Cohn SM, Ernst PB, Cominelli F, et al. The primary defect in experimental ileitis originates from a nonhematopoietic source. J Exp Med. 2006; 203:541-52. https://doi.org/10.1084/jem.20050407
110. Poritz LS, Harris LR, 3rd, Kelly AA, Koltun WA. Increase in the tight junction protein claudin-1 in intestinal inflammation. Dig Dis Sci. 2011; 56:2802-9. https://doi.org/10.1007/s10620-011-1688-9
111. Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordlinger B, Starling N. Colorectal cancer. Lancet. 2010; 375:1030-47. https://doi.org/10.1016/S0140-6736(10)60353-4
112. Kinugasa T, Huo Q, Higashi D, Shibaguchi H, Kuroki M, Tanaka T, Futami K, Yamashita Y, Hachimine K, Maekawa S, et al. Selective up-regulation of claudin-1 and claudin-2 in colorectal cancer. Anticancer Res. 2007; 27:3729-34
113. Darido C, Buchert M, Pannequin J, Bastide P, Zalzali H, Mantamadiotis T, Bourgaux JF, Garambois V, Jay P, Blache P, et al. Defective claudin-7 regulation by Tcf-4 and Sox-9 disrupts the polarity and increases the tumorigenicity of colorectal cancer cells. Cancer Res. 2008; 68:4258-68. https://doi.org/10.1158/0008-5472.CAN-07-5805
114. Matsuda M, Sentani K, Noguchi T, Hinoi T, Okajima M, Matsusaki K, Sakamoto N, Anami K, Naito Y, Oue N, et al. Immunohistochemical analysis of colorectal cancer with gastric phenotype: Claudin-18 is associated with poor prognosis. Pathol Int. 2010; 60:673-80. https://doi.org/10.1111/j.1440-1827.2010.02587.x
115. Grone J, Weber B, Staub E, Heinze M, Klaman I, Pilarsky C, Hermann K, Castanos-Velez E, Röpcke S, Mann B, et al. Differential expression of genes encoding tight junction proteins in colorectal cancer: Frequent dysregulation of claudin-1, −8 and −12. Int J Colorectal Dis. 2007; 22:651-9. https://doi.org/10.1007/s00384-006-0197-3
116. Wang L, Li SY, An P, Cai HY. [Expression and clinical significance of Claudin-1 and Claudin-4 in colorectal cancer tissues]. Zhonghua Wei Chang Wai Ke Za Zhi. 2012; 15:1073-6
117. de Souza WF, Fortunato-Miranda N, Robbs BK, de Araujo WM, de-Freitas-Junior JC, Bastos LG, Viola JP, Morgado-Díaz JA. Claudin-3 overexpression increases the malignant potential of colorectal cancer cells: Roles of ERK1/2 and PI3K-Akt as modulators of EGFR signaling. PloS One. 2013; 8:e74994. https://doi.org/10.1371/journal.pone.0074994
118. Ueda J, Semba S, Chiba H, Sawada N, Seo Y, Kasuga M, Yokozaki H. Heterogeneous expression of claudin-4 in human colorectal cancer: Decreased claudin-4 expression at the invasive front correlates cancer invasion and metastasis. Pathobiology. 2007; 74:32-41. https://doi.org/10.1159/000101049
119. Oshima T, Kunisaki C, Yoshihara K, Yamada R, Yamamoto N, Sato T, Sato T, Makino H, Yamagishi S, Nagano Y, et al. Reduced expression of the claudin-7 gene correlates with venous invasion and liver metastasis in colorectal cancer. Oncol Rep. 2008; 19:953-9
120. Huo Q, Kinugasa T, Wang L, Huang J, Zhao J, Shibaguchi H, Kuroki M, Tanaka T, Yamashita Y, Nabeshima K, et al. Claudin-1 protein is a major factor involved in the tumorigenesis of colorectal cancer. Anticancer Res. 2009; 29:851-7
121. Bornholdt J, Friis S, Godiksen S, Poulsen SS, Santoni-Rugiu E, Bisgaard HC, Lothe IM, Ikdahl T, Tveit KM, Johnson E, et al. The level of claudin-7 is reduced as an early event in colorectal carcinogenesis. BMC Cancer 2011; 11:65. https://doi.org/10.1186/1471-2407-11-65
122. Kinugasa T, Akagi Y, Ochi T, Tanaka N, Kawahara A, Ishibashi Y, Gotanda Y, Yamaguchi K, Shiratuchi I, Oka Y, et al. Increased claudin-1 protein expression in hepatic metastatic lesions of colorectal cancer. Anticancer Res. 2012; 32:2309-14
123. Maryan N, Statkiewicz M, Mikula M, Goryca K, Paziewska A, Strzalkowska A, Dabrowska M, Bujko M, Ostrowski J. Regulation of the expression of claudin 23 by the enhancer of zeste 2 polycomb group protein in colorectal cancer. Mol Med Rep. 2015; 12:728-36
124. Nakayama F, Semba S, Usami Y, Chiba H, Sawada N, Yokozaki H. Hypermethylation-modulated downregulation of claudin-7 expression promotes the progression of colorectal carcinoma. Pathobiology. 2008; 75:177-85. https://doi.org/10.1159/000124978
125. Shiou SR, Singh AB, Moorthy K, Datta PK, Washington MK, Beauchamp RD, Dhawan P. Smad4 regulates claudin-1 expression in a transforming growth factor-beta-independent manner in colon cancer cells. Cancer Res. 2007; 67:1571-9. https://doi.org/10.1158/0008-5472.CAN-06-1680
126. Singh AB, Sharma A, Smith JJ, Krishnan M, Chen X, Eschrich S, Washington MK, Yeatman TJ, Beauchamp RD, Dhawan P. Claudin-1 up-regulates the repressor ZEB-1 to inhibit E-cadherin expression in colon cancer cells. Gastroenterology. 2011; 141:2140-53. https://doi.org/10.1053/j.gastro.2011.08.038
127. Shibutani M, Noda E, Maeda K, Nagahara H, Ohtani H, Hirakawa K. Low expression of claudin-1 and presence of poorly-differentiated tumor clusters correlate with poor prognosis in colorectal cancer. Anticancer Res. 2013; 33:3301-6
128. Harpavat S, Pammi M, Gilger M. Novel treatments for NEC: Keeping IBD in mind. Curr Gastroenterol Rep. 2012; 14:373-9. https://doi.org/10.1007/s11894-012-0267-3
129. Hansson GC, Johansson ME. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Gut Microbes. 2010; 1:51-4. https://doi.org/10.4161/gmic.1.1.10470
130. Dorofeyev AE, Vasilenko IV, Rassokhina OA, Kondratiuk RB. Mucosal barrier in ulcerative colitis and Crohn's disease. Gastroenterol Res Pract. 2013; 2013:431231. https://doi.org/10.1155/2013/431231
131. Arboleya S, Ang L, Margolles A, Yiyuan L, Dongya Z, Liang X, Solís G, Fernández N, de Los Reyes-Gavilán CG, Gueimonde M. Deep 16S rRNA metagenomics and quantitative PCR analyses of the premature infant fecal microbiota. Anaerobe. 2012; 18:378-80. https://doi.org/10.1016/j.anaerobe.2012.04.013
132. Cassir N, Benamar S, Khalil JB, Croce O, Saint-Faust M, Jacquot A, Million M, Azza S, Armstrong N, Henry M, et al. Clostridium butyricum Strains and Dysbiosis Linked to Necrotizing Enterocolitis in Preterm Neonates. Clin Infect Dis. 2015; 61:1107-15. https://doi.org/10.1093/cid/civ468
133. Ward DV, Scholz M, Zolfo M, Taft DH, Schibler KR, Tett A, Segata N, Morrow AL. Metagenomic Sequencing with Strain-Level Resolution Implicates Uropathogenic E. coli in Necrotizing Enterocolitis and Mortality in Preterm Infants. Cell Rep. 2016; 14:2912-24
134. Azcarate-Peril MA, Foster DM, Cadenas MB, Stone MR, Jacobi SK, Stauffer SH, Pease A, Gookin JL. Acute necrotizing enterocolitis of preterm piglets is characterized by dysbiosis of ileal mucosa-associated bacteria. Gut Microbes 2011; 2:234-43. https://doi.org/10.4161/gmic.2.4.16332
135. Loh G, Blaut M. Role of commensal gut bacteria in Inflamm Bowel Dis. Gut Microbes. 2012; 3:544-55. https://doi.org/10.4161/gmic.22156
136. Yadav V, Varum F, Bravo R, Furrer E, Bojic D, Basit AW. Inflammatory bowel disease: Exploring gut pathophysiology for novel therapeutic targets. Transl Res. 2016; 176:38-68. https://doi.org/10.1016/j.trsl.2016.04.009
137. Hunter CJ, De Plaen IG. Inflammatory signaling in NEC: Role of NF-kappaB, cytokines and other inflammatory mediators. Pathophysiology. 2014; 21:55-65. https://doi.org/10.1016/j.pathophys.2013.11.010
138. Emami CN, Chokshi N, Wang J, Hunter C, Guner Y, Goth K, Wang L, Grishin A, Ford HR. Role of interleukin-10 in the pathogenesis of necrotizing enterocolitis. Am J Surg 2012; 203:428-35. https://doi.org/10.1016/j.amjsurg.2011.08.016
139. Kling KM, Kirby L, Kwan KY, Kim F, McFadden DW. Interleukin-10 inhibits inducible nitric oxide synthase in an animal model of necrotizing enterocolitis. Int J Surg Invest. 1999; 1:337-42
140. Nadler EP, Stanford A, Zhang XR, Schall LC, Alber SM, Watkins SC, Ford HR. Intestinal cytokine gene expression in infants with acute necrotizing enterocolitis: Interleukin-11 mRNA expression inversely correlates with extent of disease. J Pediatr Surg. 2001; 36:1122-9. https://doi.org/10.1053/jpsu.2001.25726
141. Scharl M, Paul G, Barrett KE, McCole DF. AMP-activated protein kinase mediates the interferon-gamma-induced decrease in intestinal epithelial barrier function. J Biol Chem. 2009; 284:27952-63. https://doi.org/10.1074/jbc.M109.046292
142. Sato Y, Takahashi S, Kinouchi Y, Shiraki M, Endo K, Matsumura Y, Kakuta Y, Tosa M, Motida A, Abe H, et al. IL-10 deficiency leads to somatic mutations in a model of IBD. Carcinogenesis. 2006; 27:1068-73. https://doi.org/10.1093/carcin/bgi327
143. Li MC, He SH. IL-10 and its related cytokines for treatment of inflammatory bowel disease. World J Gastroenterol. 2004; 10:620-5. https://doi.org/10.3748/wjg.v10.i5.620
144. Tremblay E, Thibault MP, Ferretti E, Babakissa C, Bertelle V, Bettolli M, Burghardt KM, Colombani JF, Grynspan D, Levy E, et al. Gene expression profiling in necrotizing enterocolitis reveals pathways common to those reported in Crohn's disease. BMC Med Genom. 2016; 9:6. https://doi.org/10.1186/s12920-016-0166-9
145. Rosenstiel P, Fantini M, Brautigam K, Kuhbacher T, Waetzig GH, Seegert D, Schreiber S. TNF-alpha and IFN-gamma regulate the expression of the NOD2 (CARD15) gene in human intestinal epithelial cells. Gastroenterology. 2003; 124:1001-9. https://doi.org/10.1053/gast.2003.50157
146. Zouali H, Bonnard A, De Lagausie DL, Farnoux C, Aigrain Y, Cezard JP, Cezard JP, Peuchmaur M, Hugot JP, Berrebi D. CARD15/NOD2 is not a predisposing factor for necrotizing enterocolitis. Dig Dis Sci. 2005; 50:1684-7. https://doi.org/10.1007/s10620-005-2915-z
147. Hartel C, Hartz A, Pagel J, Rupp J, Stein A, Kribs A, et al. NOD2 Loss-of-Function Mutations and Risks of Necrotizing Enterocolitis or Focal Intestinal Perforation in Very Low-birth-weight Infants. Inflamm Bowel Dis. 2016; 22:249-56. https://doi.org/10.1097/MIB.0000000000000658