Celiac disease histopathology recapitulates hedgehog downregulation, consistent with wound healing processes activation

PLoS ONE

Volumn 10, Issue 12, 2015, Pages

  Senger, Stefania ^a   Sapone, Anna ^a,b   Fiorentino, Maria Rosaria ^a   Mazzarella, Giuseppe ^c   Lauwers, Gregory Y ^a   Fasano, Alessio ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c CNR   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

BONE MORPHOGENETIC PROTEIN 4; CELL MARKER; G PROTEIN COUPLED RECEPTOR; LEUCIN RICH REPEAT CONTAINING G PROTEIN COUPLED RECEPTOR 5; SONIC HEDGEHOG PROTEIN; UNCLASSIFIED DRUG; WNT PROTEIN; BMP4 PROTEIN, HUMAN; BONE MORPHOGENETIC PROTEIN; GREM1 PROTEIN, HUMAN; GREM2 PROTEIN, HUMAN; SIGNAL PEPTIDE;

ACUTE DISEASE; ADULT; AGED; ARTICLE; CELIAC DISEASE; CELL EXPANSION; CLINICAL ARTICLE; CONTROLLED STUDY; DOWN REGULATION; FEMALE; GENE; GREMLIN 1 GENE; GREMLIN 2 GENE; HISTOPATHOLOGY; HUMAN; HUMAN CELL; HUMAN TISSUE; HYPERPLASIA; IMMUNOHISTOCHEMISTRY; IN SITU HYBRIDIZATION; INTESTINAL STEM CELL; INTESTINE BIOPSY; INTESTINE CRYPT; LAMINA PROPRIA; MALE; MESENCHYMAL STEM CELL; QUANTITATIVE ANALYSIS; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; STEM CELL NICHE; UPREGULATION; WOUND HEALING; ANIMAL; CASE CONTROL STUDY; CELL DIFFERENTIATION; CELL PROLIFERATION; EPITHELIUM CELL; INTESTINE MUCOSA; METABOLISM; MOUSE; PATHOLOGY; PHYSIOLOGY; REGENERATION; SMALL INTESTINE; STEM CELL; WNT SIGNALING;

ANIMALS; BONE MORPHOGENETIC PROTEIN 4; BONE MORPHOGENETIC PROTEINS; CASE-CONTROL STUDIES; CELIAC DISEASE; CELL DIFFERENTIATION; CELL PROLIFERATION; DOWN-REGULATION; EPITHELIAL CELLS; HEDGEHOG PROTEINS; HUMANS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; INTESTINAL MUCOSA; INTESTINE, SMALL; MICE; REGENERATION; STEM CELLS; WNT SIGNALING PATHWAY; WOUND HEALING;

EID: 84955609854     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0144634     Document Type: Article

References (42)

1. Madison BB, Braunstein K, Kuizon E, Portman K, Qiao XT, Gumucio DL. Epithelial hedgehog signals pattern the intestinal crypt-villus axis. Development. 2005; 132(2): 279-89. doi: 10.1242/dev.01576 PMID: 15590741.
2. Haramis AP, Begthel H, Van Den Born M, van Es J, Jonkheer S, Offerhaus GJ, et al. De novo crypt formation and juvenile polyposis on BMP inhibition in mouse intestine. Science. 2004; 303(5664): 1684-6. doi: 10.1126/science.1093587 PMID: 15017003.
3. van Dop WA, Heijmans J, Buller NV, Snoek SA, Rosekrans SL, Wassenberg EA, et al. Loss of Indian Hedgehog activates multiple aspects of a wound healing response in the mouse intestine. Gastroenterology. 2010; 139(5): 1665-76, 76 e1-10. doi: 10.1053/j.gastro.2010.07.045 PMID: 20682322.
4. Roberts DJ, Johnson RL, Burke AC, Nelson CE, Morgan BA, Tabin C. Sonic hedgehog is an endodermal signal inducing Bmp-4 and Hox genes during induction and regionalization of the chick hindgut. Development. 1995; 121(10): 3163-74. PMID: 7588051.
5. Roberts DJ, Smith DM, Goff DJ, Tabin CJ. Epithelial-mesenchymal signaling during the regionalization of the chick gut. Development. 1998; 125(15): 2791-801. PMID: 9655802.
6. Sukegawa A, Narita T, Kameda T, Saitoh K, Nohno T, Iba H, et al. The concentric structure of the developing gut is regulated by Sonic hedgehog derived from endodermal epithelium. Development. 2000; 127(9): 1971-80. PMID: 10751185.
7. Vanuytsel T, Senger S, Fasano A, Shea-Donohue T. Major signaling pathways in intestinal stem cells. Biochimica et biophysica acta. 2013; 1830(2): 2410-26. doi: 10.1016/j.bbagen.2012.08.006 PMID: 22922290; PubMed Central PMCID: PMC4408610.
8. Zacharias WJ, Li X, Madison BB, Kretovich K, Kao JY, Merchant JL, et al. Hedgehog is an anti-inflammatory epithelial signal for the intestinal lamina propria. Gastroenterology. 2010; 138(7): 2368-77, 77 e1-4. doi: 10.1053/j.gastro.2010.02.057 PMID: 20206176; PubMed Central PMCID: PMC2883680.
9. Kosinski C, Stange DE, Xu C, Chan AS, Ho C, Yuen ST, et al. Indian hedgehog regulates intestinal stem cell fate through epithelial-mesenchymal interactions during development. Gastroenterology. 2010; 139(3): 893-903. doi: 10.1053/j.gastro.2010.06.014 PMID: 20542037; PubMed Central PMCID: PMC2930094.
10. Zacharias WJ, Madison BB, Kretovich KE, Walton KD, Richards N, Udager AM, et al. Hedgehog signaling controls homeostasis of adult intestinal smooth muscle. Developmental biology. 2011; 355(1): 152-62. doi: 10.1016/j.ydbio.2011.04.025 PMID: 21545794; PubMed Central PMCID: PMC3118277.
11. Marsh MN. Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity ('celiac sprue'). Gastroenterology. 1992; 102 (1): 330-54. PMID: 1727768.
12. Savidge TC, Shmakov AN, Walker-Smith JA, Phillips AD. Epithelial cell proliferation in childhood enteropathies. Gut. 1996; 39(2): 185-93. PMID: 8977336; PubMed Central PMCID: PMC1383296.
13. Savidge TC, Walker-Smith JA, Phillips AD, Savidge TC. Intestinal proliferation in coeliac disease: Looking into the crypt. Gut. 1995; 36(3): 321-3. PMID: 7698683; PubMed Central PMCID: PMC1382435.
14. Liang R, Hinds R, Abud HE, Cheng W. Hedgehog signalling is downregulated in celiac disease. Canadian Journal of gastroenterology = Journal canadien de gastroenterologie. 2013; 27(1): E5-7. PMID: 23378984; PubMed Central PMCID: PMC3545627.
15. Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nature protocols. 2008; 3(6): 1101-8. PMID: 18546601.
16. Buller NV, Rosekrans SL, Westerlund J, Van Den Brink GR. Hedgehog signaling and maintenance of homeostasis in the intestinal epithelium. Physiology. 2012; 27(3): 148-55. doi: 10.1152/physiol.00003. 2012 PMID: 22689790.
17. Verbeke S, Gotteland M, Fernandez M, Bremer J, Rios G, Brunser O. Basement membrane and connective tissue proteins in intestinal mucosa of patients with coeliac disease. Journal of clinical pathology. 2002; 55(6): 440-5. PMID: 12037027; PubMed Central PMCID: PMC1769663.
18. Mifflin RC, Pinchuk IV, Saada JI, Powell DW. Intestinal myofibroblasts: Targets for stem cell therapy. American Journal of physiology Gastrointestinal and liver physiology. 2011; 300(5): G684-96. doi: 10.1152/ajpgi.00474.2010 PMID: 21252048; PubMed Central PMCID: PMC3094146.
19. Kosinski C, Li VS, Chan AS, Zhang J, Ho C, Tsui WY, et al. Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors. Proceedings of the National Academy of Sciences of the United States of America. 2007; 104(39): 15418-23. doi: 10.1073/pnas.0707210104 PMID: 17881565; PubMed Central PMCID: PMC2000506.
20. Barker N, van Es JH, Kuipers J, Kujala P, Van Den Born M, Cozijnsen M, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature. 2007; 449(7165): 1003-7. doi: 10.1038/nature06196 PMID: 17934449.
21. Barker N, van Oudenaarden A, Clevers H. Identifying the stem cell of the intestinal crypt: Strategies and pitfalls. Cell stem cell. 2012; 11(4): 452-60. doi: 10.1016/j.stem.2012.09.009 PMID: 23040474.
22. Snippert HJ, van Es JH, Van Den Born M, Begthel H, Stange DE, Barker N, et al. Prominin-1/CD133 marks stem cells and early progenitors in mouse small intestine. Gastroenterology. 2009; 136(7): 2187-94 e1. doi: 10.1053/j.gastro.2009.03.002 PMID: 19324043.
23. Blache P, van de Wetering M, Duluc I, Domon C, Berta P, Freund JN, et al. SOX9 is an intestine crypt transcription factor, is regulated by the Wnt pathway, and represses the CDX2 and MUC2 genes. The Journal of Cell Biology. 2004; 166(1): 37-47. doi: 10.1083/jcb.200311021 PMID: 15240568; PubMed Central PMCID: PMC2172132.
24. Bajaj-Elliott M, Poulsom R, Pender SL, Wathen NC, MacDonald TT. Interactions between stromal cell -derived keratinocyte growth factor and epithelial transforming growth factor in immune-mediated crypt cell hyperplasia. The Journal of clinical investigation. 1998; 102(8): 1473-80. doi: 10.1172/JCI2792 PMID: 9788959; PubMed Central PMCID: PMC508996.
25. Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature. 2009; 459(7244): 262-5. doi: 10.1038/nature07935 PMID: 19329995.
26. Jung P, Sato T, Merlos-Suarez A, Barriga FM, Iglesias M, Rossell D, et al. Isolation and in vitro expansion of human colonic stem cells. Nature Medicine. 2011; 17(10): 1225-7. doi: 10.1038/nm.2470 PMID: 21892181.
27. Zuniga A, Laurent F, Lopez-Rios J, Klasen C, Matt N, Zeller R. Conserved cis-regulatory regions in a large genomic landscape control SHH and BMP-regulated Gremlin1 expression in mouse limb buds. BMC developmental biology. 2012; 12: 23. doi: 10.1186/1471-213X-12-23 PMID: 22888807; PubMed Central PMCID: PMC3541112.
28. Simmons JG, Pucilowska JB, Keku TO, Lund PK. IGF-I and TGF-beta1 have distinct effects on phenotype and proliferation of intestinal fibroblasts. American Journal of physiology Gastrointestinal and liver physiology. 2002; 283(3): G809-18. doi: 10.1152/ajpgi.00057.2002 PMID: 12181198.
29. Powell DW, Adegboyega PA, Di Mari JF, Mifflin RC. Epithelial cells and their neighbors I. Role of intestinal myofibroblasts in development, repair, and cancer. American Journal of physiology Gastrointestinal and liver physiology. 2005; 289(1): G2-7. doi: 10.1152/ajpgi.00075.2005 PMID: 15961883.
30. Selby WS, Janossy G, Bofill M, Jewell DP. Lymphocyte subpopulations in the human small intestine. The findings in normal mucosa and in the mucosa of patients with adult coeliac disease. Clinical and experimental Immunology. 1983; 52(1): 219-28. PMID: 6345034; PubMed Central PMCID: PMC1535584.
31. Lundin KE, Scott H, Hansen T, Paulsen G, Halstensen TS, Fausa O, et al. Gliadin-specific, HLA-DQ (alpha 1. 0501, beta 1. 0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients. The Journal of experimental Medicine. 1993; 178(1): 187-96. PMID: 8315377; PubMed Central PMCID: PMC2191064.
32. Ciccocioppo R, Di Sabatino A, Bauer M, Della Riccia DN, Bizzini F, Biagi F, et al. Matrix metalloproteinase pattern in celiac duodenal mucosa. Laboratory investigation; a Journal of technical methods and pathology. 2005; 85(3): 397-407. doi: 10.1038/labinvest.3700225 PMID: 15608660.
33. Nilsen EM, Lundin KE, Krajci P, Scott H, Sollid LM, Brandtzaeg P. Gluten specific, HLA-DQ restricted T cells from coeliac mucosa produce cytokines with Th1 or Th0 profile dominated by interferon gamma. Gut. 1995; 37(6): 766-76. PMID: 8537046; PubMed Central PMCID: PMC1382937.
34. Shi Z, Rockey DC. Interferon-gamma-mediated inhibition of serum response factor-dependent smooth muscle-specific gene expression. The Journal of Biological Chemistry. 2010; 285(42): 32415-24. doi: 10.1074/jbc.M110.164863 PMID: 20685657; PubMed Central PMCID: PMC2952243.
35. Owens GK, Kumar MS, Wamhoff BR. Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev. 2004; 84(3): 767-801. doi: 10.1152/physrev.00041.2003 PMID: 15269336.
36. Hinz B, Phan SH, Thannickal VJ, Galli A, Bochaton-Piallat ML, Gabbiani G. The myofibroblast: One function, multiple origins. The American Journal of pathology. 2007; 170(6): 1807-16. doi: 10.2353/ajpath.2007.070112 PMID: 17525249; PubMed Central PMCID: PMCPMC1899462.
37. Capuano M, Iaffaldano L, Tinto N, Montanaro D, Capobianco V, Izzo V, et al. MicroRNA-449a overexpression, reduced NOTCH1 signals and scarce goblet cells characterize the small intestine of celiac patients. PloS one. 2011; 6(12): E29094. doi: 10.1371/Journal.pone.0029094 PMID: 22194996; PubMed Central PMCID: PMC3240641.
38. Bardella MT, Velio P, Cesana BM, Prampolini L, Casella G, Di Bella C, et al. Coeliac disease: A histological follow-up study. Histopathology. 2007; 50(4): 465-71. doi: 10.1111/j.1365-2559.2007.02621.x PMID: 17448022.
39. Lanzini A, Lanzarotto F, Villanacci V, Mora A, Bertolazzi S, Turini D, et al. Complete recovery of intestinal mucosa occurs very rarely in adult coeliac patients despite adherence to gluten-free diet. Alimentary pharmacology & therapeutics. 2009; 29(12): 1299-308. doi: 10.1111/j.1365-2036.2009.03992.x PMID: 19302264.
40. Malamut G, Cellier C. Complications of coeliac disease. Best Pract Res Clin Gastroenterol. 2015; 29 (3): 451-8. doi: 10.1016/j.bpg.2015.05.005 PMID: 26060109.
41. Korpe PS, Petri WA Jr. Environmental enteropathy: Critical implications of a poorly understood condition. Trends in molecular Medicine. 2012; 18(6): 328-36. doi: 10.1016/j.molmed.2012.04.007 PMID: 22633998; PubMed Central PMCID: PMCPMC3372657.
42. Gentile NM, Murray JA, Pardi DS. Autoimmune enteropathy: A review and update of clinical management. Curr Gastroenterol Rep. 2012; 14(5): 380-5. doi: 10.1007/s11894-012-0276-2 PMID: 22810979; PubMed Central PMCID: PMCPMC3912565.