Fibroblasts and myofibroblasts of the intestinal lamina propria in physiology and disease

Differentiation

Volumn 92, Issue 3, 2016, Pages 116-131

  Roulis, Manolis ^a   Flavell, Richard A ^a  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Fibroblast; Lamina propria mesenchyme; Myofibroblast; Stromal cells

Indexed keywords

ALPHA SMOOTH MUSCLE ACTIN; BONE MORPHOGENETIC PROTEIN; FIBROBLAST GROWTH FACTOR; NOTCH RECEPTOR; PLATELET DERIVED GROWTH FACTOR A; SONIC HEDGEHOG PROTEIN; TRANSFORMING GROWTH FACTOR BETA;

ANTIGEN PRESENTATION; CANCER ASSOCIATED FIBROBLAST; CARCINOGENESIS; CELL HETEROGENEITY; CELL INTERACTION; COLORECTAL CANCER; CROHN DISEASE; DEXTRAN SODIUM SULFATE-INDUCED COLITIS; EPITHELIAL MESENCHYMAL TRANSITION; EXTRACELLULAR MATRIX; FIBROBLAST; HUMAN; IMMUNOREGULATION; INFLAMMATORY BOWEL DISEASE; INNATE IMMUNITY; INTESTINAL FIBROSIS; INTESTINAL STEM CELL; INTESTINE EPITHELIUM CELL; LAMINA PROPRIA; MESENCHYME CELL; MUCOSAL IMMUNITY; MYOFIBROBLAST; NONHUMAN; ORGANOGENESIS; PRIORITY JOURNAL; REVIEW; STEM CELL NICHE; ULCERATIVE COLITIS; ANIMAL; CYTOLOGY; INTESTINE; INTESTINE MUCOSA; MESODERM; METABOLISM; PATHOLOGY; PATHOPHYSIOLOGY; STROMA CELL;

ANIMALS; FIBROBLASTS; HUMANS; INTESTINAL MUCOSA; INTESTINES; MESODERM; MYOFIBROBLASTS; STROMAL CELLS;

EID: 84975511698     PISSN: 03014681     EISSN: 14320436     Source Type: Journal    
DOI: 10.1016/j.diff.2016.05.002     Document Type: Review

References (131)

1. Al Alam, D., Sala, F.G., Baptista, S., Galzote, R., Danopoulos, S., Tiozzo, C., Gage, P., Grikscheit, T., Warburton, D., Frey, M.R., Bellusci, S., FGF9–Pitx2–FGF10 signaling controls cecal formation in mice. Dev. Biol. 369 (2012), 340–348.
2. Andrae, J., Gallini, R., Betsholtz, C., Role of platelet-derived growth factors in physiology and medicine. Genes Dev. 22 (2008), 1276–1312.
3. Armaka, M., Apostolaki, M., Jacques, P., Kontoyiannis, D.L., Elewaut, D., Kollias, G., Mesenchymal cell targeting by TNF as a common pathogenic principle in chronic inflammatory joint and intestinal diseases. J. Exp. Med. 205 (2008), 331–337.
4. Artells, R., Navarro, A., Diaz, T., Monzó, M., Ultrastructural and immunohistochemical analysis of intestinal myofibroblasts during the early organogenesis of the human small intestine. Anat. Rec.: Adv. Integr. Anat. Evolut. Biol. 294 (2011), 462–471.
5. Bamba, S., Andoh, A., Yasui, H., Araki, Y., Bamba, T., Fujiyama, Y., Matrix metalloproteinase-3 secretion from human colonic subepithelial myofibroblasts: role of interleukin-17. J. Gastroenterol. 38 (2003), 548–554.
6. Bamias, G., Jia, L.G., Cominelli, F., The tumor necrosis factor-like cytokine 1A/death receptor 3 cytokine system in intestinal inflammation. Curr. Opin. Gastroenterol. 29 (2013), 597–602.
7. Barker, N., Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration. Nat. Rev. Mol. Cell Biol. 15 (2014), 19–33.
8. Batts, L.E., Polk, D.B., Dubois, R.N., Kulessa, H., Bmp signaling is required for intestinal growth and morphogenesis. Dev. Dyn. 235 (2006), 1563–1570.
9. Beswick, E.J., Johnson, J.R., Saada, J.I., Humen, M., House, J., Dann, S., Qiu, S., Brasier, A.R., Powell, D.W., Reyes, V.E., Pinchuk, I.V., TLR4 activation enhances the PD-L1-mediated tolerogenic capacity of colonic CD90+ stromal cells. J. Immunol. 193 (2014), 2218–2229.
10. Bhowmick, N.A., Chytil, A., Plieth, D., Gorska, A.E., Dumont, N., Shappell, S., Washington, M.K., Neilson, E.G., Moses, H.L., TGF-beta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia. Science 303 (2004), 848–851.
11. Brown, S.L., Riehl, T.E., Walker, M.R., Geske, M.J., Doherty, J.M., Stenson, W.F., Stappenbeck, T.S., Myd88-dependent positioning of Ptgs2-expressing stromal cells maintains colonic epithelial proliferation during injury. J. Clin. Investig. 117 (2007), 258–269.
12. Calloni, G.W., Glavieux-Pardanaud, C., Le Douarin, N.M., Dupin, E., Sonic Hedgehog promotes the development of multipotent neural crest progenitors endowed with both mesenchymal and neural potentials. Proc. Natl. Acad. Sci. USA 104 (2007), 19879–19884.
13. Calon, A., Espinet, E., Palomo-Ponce, S., Tauriello, Daniele, V.F., Iglesias, M., Céspedes, María, V., Sevillano, M., Nadal, C., Jung, P., Zhang, Xiang, H.F., Byrom, D., Riera, A., Rossell, D., Mangues, R., Massagué, J., Sancho, E., Batlle, E., Dependency of colorectal cancer on a TGF-β-driven program in stromal cells for metastasis initiation. Cancer Cell 22 (2012), 571–584.
14. Calon, A., Lonardo, E., Berenguer-Llergo, A., Espinet, E., Hernando-Momblona, X., Iglesias, M., Sevillano, M., Palomo-Ponce, S., Tauriello, D.V., Byrom, D., Cortina, C., Morral, C., Barcelo, C., Tosi, S., Riera, A., Attolini, C.S., Rossell, D., Sancho, E., Batlle, E., Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nat. Genet. 47 (2015), 320–329.
15. Catarzi, S., Favilli, F., Romagnoli, C., Marcucci, T., Picariello, L., Tonelli, F., Vincenzini, M.T., Iantomasi, T., Oxidative state and IL-6 production in intestinal myofibroblasts of Crohn's disease patients. Inflamm. Bowel Dis. 17 (2011), 1674–1684.
16. Chivukula, R.R., Shi, G., Acharya, A., Mills, E.W., Zeitels, L.R., Anandam, J.L., Abdelnaby, A.A., Balch, G.C., Mansour, J.C., Yopp, A.C., Maitra, A., Mendell, J.T., An essential mesenchymal function for miR-143/145 in intestinal epithelial regeneration. Cell 157 (2014), 1104–1116.
17. Clevers, H., The intestinal crypt, A prototype stem. Cell Compart. Cell 154 (2013), 274–284.
18. Desaki, J., Shimizu, M., A re-examination of the cellular reticulum of fibroblast-like cells in the rat small intestine by scanning electron microscopy. J. Electron Microsc. 49 (2000), 203–208.
19. Desmouliere, A., Chaponnier, C., Gabbiani, G., Tissue repair, contraction, and the myofibroblast. Wound Repair Regen. 13 (2005), 7–12.
20. Di Mari, J.F., Mifflin, R.C., Adegboyega, P.A., Saada, J.I., Powell, D.W., IL-1alpha-induced COX-2 expression in human intestinal myofibroblasts is dependent on a PKCzeta-ROS pathway. Gastroenterology 124 (2003), 1855–1865.
21. Di Sabatino, A., Pender, S.L., Jackson, C.L., Prothero, J.D., Gordon, J.N., Picariello, L., Rovedatti, L., Docena, G., Monteleone, G., Rampton, D.S., Tonelli, F., Corazza, G.R., MacDonald, T.T., Functional modulation of Crohn's disease myofibroblasts by anti-tumor necrosis factor antibodies. Gastroenterology 133 (2007), 137–149.
22. Dupin, E., Sommer, L., Neural crest progenitors and stem cells: from early development to adulthood. Dev. Biol. 366 (2012), 83–95.
23. Eyden, B., The myofibroblast: phenotypic characterization as a prerequisite to understanding its functions in translational medicine. J. Cell. Mol. Med. 12 (2008), 22–37.
24. Eyden, B., Curry, A., Wang, G., Stromal cells in the human gut show ultrastructural features of fibroblasts and smooth muscle cells but not myofibroblasts. J. Cell. Mol. Med. 15 (2011), 1483–1491.
25. Fagarasan, S., Kinoshita, K., Muramatsu, M., Ikuta, K., Honjo, T., In situ class switching and differentiation to IgA-producing cells in the gut lamina propria. Nature 413 (2001), 639–643.
26. Farin, H.F., Van Es, J.H., Clevers, H., Redundant sources of Wnt regulate intestinal stem cells and promote formation of Paneth Cells. Gastroenterology 143 (2012), 1518–1529 e1517.
27. Fevr, T., Robine, S., Louvard, D., Huelsken, J., Wnt/beta-catenin is essential for intestinal homeostasis and maintenance of intestinal stem cells. Mol. Cell. Biol. 27 (2007), 7551–7559.
28. Flier, S.N., Tanjore, H., Kokkotou, E.G., Sugimoto, H., Zeisberg, M., Kalluri, R., Identification of epithelial to mesenchymal transition as a novel source of fibroblasts in intestinal fibrosis. J. Biol. Chem. 285 (2010), 20202–20212.
29. Fontani, F., Marcucci, T., Picariello, L., Tonelli, F., Vincenzini, M.T., Iantomasi, T., Redox regulation of MMP-3/TIMP-1 ratio in intestinal myofibroblasts: effect of N-acetylcysteine and curcumin. Exp. cell Res. 323 (2014), 77–86.
30. Furuya, S., Furuya, K., Subepithelial fibroblasts in intestinal villi: roles in intercellular communication. Int. Rev. Cytol. 264 (2007), 165–223.
31. Gabbiani, G., Ryan, G.B., Majne, G., Presence of modified fibroblasts in granulation tissue and their possible role in wound contraction. Experientia 27 (1971), 549–550.
32. Geske, M.J., Zhang, X., Patel, K.K., Ornitz, D.M., Stappenbeck, T.S., Fgf9 signaling regulates small intestinal elongation and mesenchymal development. Development 135 (2008), 2959–2968.
33. Goessling, W., North, T.E., Loewer, S., Lord, A.M., Lee, S., Stoick-Cooper, C.L., Weidinger, G., Puder, M., Daley, G.Q., Moon, R.T., Zon, L.I., Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell 136 (2009), 1136–1147.
34. Goruppi, S., Dotto, G.P., Mesenchymal stroma: primary determinant and therapeutic target for epithelial cancer. Trends Cell Biol. 23 (2013), 593–602.
35. Gregorieff, A., Pinto, D., Begthel, H., Destree, O., Kielman, M., Clevers, H., Expression pattern of Wnt signaling components in the adult intestine. Gastroenterology 129 (2005), 626–638.
36. Greten, F.R., Eckmann, L., Greten, T.F., Park, J.M., Li, Z.W., Egan, L.J., Kagnoff, M.F., Karin, M., IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118 (2004), 285–296.
37. Grillo, A.R., Scarpa, M., D'Incà, R., Brun, P., Scarpa, M., Porzionato, A., De Caro, R., Martines, D., Buda, A., Angriman, I., Palù, G., Sturniolo, G.C., Castagliuolo, I., TAK1 is a key modulator of the profibrogenic phenotype of human ileal myofibroblasts in Crohn's disease. Am. J. Physiol.: Gastrointest. Liver Physiol. 309 (2015), G443–G454.
38. Hamilton, K.E., Chatterji, P., Lundsmith, E.T., Andres, S.F., Giroux, V., Hicks, P.D., Noubissi, F.K., Spiegelman, V.S., Rustgi, A.K., Loss of stromal IMP1 promotes a tumorigenic microenvironment in the colon. Mol. Cancer Res. 13 (2015), 1478–1486.
39. Haramis, A.-P.G., Begthel, H., van den Born, M., van Es, J., Jonkheer, S., Offerhaus, G.J.A., Clevers, H., De novo crypt formation and juvenile polyposis on BMP inhibition in mouse intestine. Science 303 (2004), 1684–1686.
40. Hata, K., Andoh, A., Shimada, M., Fujino, S., Bamba, S., Araki, Y., Okuno, T., Fujiyama, Y., Bamba, T., IL-17 stimulates inflammatory responses via NF-kappaB and MAP kinase pathways in human colonic myofibroblasts. Am. J. Physiol. 282 (2002), G1035–G1044.
41. Hawinkels, L.J., Paauwe, M., Verspaget, H.W., Wiercinska, E., van der Zon, J.M., van der Ploeg, K., Koelink, P.J., Lindeman, J.H., Mesker, W., ten Dijke, P., Sier, C.F., Interaction with colon cancer cells hyperactivates TGF-beta signaling in cancer-associated fibroblasts. Oncogene 33 (2014), 97–107.
42. He, X.C., Zhang, J., Tong, W.-G., Tawfik, O., Ross, J., Scoville, D.H., Tian, Q., Zeng, X., He, X., Wiedemann, L.M., Mishina, Y., Li, L., BMP signaling inhibits intestinal stem cell self-renewal through suppression of Wnt-[beta]-catenin signaling. Nat. Genet. 36 (2004), 1117–1121.
43. Heinrich, M.C., Corless, C.L., Duensing, A., McGreevey, L., Chen, C.J., Joseph, N., Singer, S., Griffith, D.J., Haley, A., Town, A., Demetri, G.D., Fletcher, C.D., Fletcher, J.A., PDGFRA activating mutations in gastrointestinal stromal tumors. Science 299 (2003), 708–710.
44. Hinz, B., The myofibroblast: paradigm for a mechanically active cell. J. Biomech. 43 (2010), 146–155.
45. Isella, C., Terrasi, A., Bellomo, S.E., Petti, C., Galatola, G., Muratore, A., Mellano, A., Senetta, R., Cassenti, A., Sonetto, C., Inghirami, G., Trusolino, L., Fekete, Z., De Ridder, M., Cassoni, P., Storme, G., Bertotti, A., Medico, E., Stromal contribution to the colorectal cancer transcriptome. Nat. Genet. 47 (2015), 312–319.
46. Johnson, L.A., Rodansky, E.S., Sauder, K.L., Horowitz, J.C., Mih, J.D., Tschumperlin, D.J., Higgins, P.D., Matrix stiffness corresponding to strictured bowel induces a fibrogenic response in human colonic fibroblasts. Inflamm. Bowel Dis. 19 (2013), 891–903.
47. Jostins, L., Ripke, S., Weersma, R.K., Duerr, R.H., McGovern, D.P., Hui, K.Y., Lee, J.C., Schumm, L.P., Sharma, Y., Anderson, C.A., Essers, J., Mitrovic, M., Ning, K., Cleynen, I., Theatre, E., Spain, S.L., Raychaudhuri, S., Goyette, P., Wei, Z., Abraham, C., Achkar, J.P., Ahmad, T., Amininejad, L., Ananthakrishnan, A.N., Andersen, V., Andrews, J.M., Baidoo, L., Balschun, T., Bampton, P.A., Bitton, A., Boucher, G., Brand, S., Buning, C., Cohain, A., Cichon, S., D'Amato, M., De Jong, D., Devaney, K.L., Dubinsky, M., Edwards, C., Ellinghaus, D., Ferguson, L.R., Franchimont, D., Fransen, K., Gearry, R., Georges, M., Gieger, C., Glas, J., Haritunians, T., Hart, A., Hawkey, C., Hedl, M., Hu, X., Karlsen, T.H., Kupcinskas, L., Kugathasan, S., Latiano, A., Laukens, D., Lawrance, I.C., Lees, C.W., Louis, E., Mahy, G., Mansfield, J., Morgan, A.R., Mowat, C., Newman, W., Palmieri, O., Ponsioen, C.Y., Potocnik, U., Prescott, N.J., Regueiro, M., Rotter, J.I., Russell, R.K., Sanderson, J.D., Sans, M., Satsangi, J., Schreiber, S., Simms, L.A., Sventoraityte, J., Targan, S.R., Taylor, K.D., Tremelling, M., Verspaget, H.W., De Vos, M., Wijmenga, C., Wilson, D.C., Winkelmann, J., Xavier, R.J., Zeissig, S., Zhang, B., Zhang, C.K., Zhao, H., International, I.B.D.G.C., Silverberg, M.S., Annese, V., Hakonarson, H., Brant, S.R., Radford-Smith, G., Mathew, C.G., Rioux, J.D., Schadt, E.E., Daly, M.J., Franke, A., Parkes, M., Vermeire, S., Barrett, J.C., Cho, J.H., Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491 (2012), 119–124.
48. Joyce, N.C., Haire, M.F., Palade, G.E., Morphologic and biochemical evidence for a contractile cell network within the rat intestinal mucosa. Gastroenterology 92 (1987), 68–81.
49. Jung, P., Sato, T., Merlos-Suarez, A., Barriga, F.M., Iglesias, M., Rossell, D., Auer, H., Gallardo, M., Blasco, M.A., Sancho, E., Clevers, H., Batlle, E., Isolation and in vitro expansion of human colonic stem cells. Nat. Med. 17 (2011), 1225–1227.
50. Kabiri, Z., Greicius, G., Madan, B., Biechele, S., Zhong, Z., Zaribafzadeh, H., Edison, Aliyev, J., Wu, Y., Bunte, R., Williams, B.O., Rossant, J., Virshup, D.M., Stroma provides an intestinal stem cell niche in the absence of epithelial Wnts. Development 141 (2014), 2206–2215.
51. Kalluri, R., Zeisberg, M., Fibroblasts in cancer. Nat. Rev. Cancer 6 (2006), 392–401.
52. Karlsson, L., Lindahl, P., Heath, J.K., Betsholtz, C., Abnormal gastrointestinal development in PDGF-A and PDGFR-(alpha) deficient mice implicates a novel mesenchymal structure with putative instructive properties in villus morphogenesis. Development 127 (2000), 3457–3466.
53. Kaser, A., Zeissig, S., Blumberg, R.S., Inflammatory bowel disease. Annu Rev. Immunol. 28 (2010), 573–621.
54. Kawamura, T., Andoh, A., Nishida, A., Shioya, M., Yagi, Y., Nishimura, T., Hashimoto, T., Tsujikawa, T., Yasui, H., Fujiyama, Y., Inhibitory effects of short-chain fatty acids on matrix metalloproteinase secretion from human colonic subepithelial myofibroblasts. Dig. Dis. Sci. 54 (2009), 238–245.
55. Kikuchi, A., Yamamoto, H., Sato, A., Matsumoto, S., New insights into the mechanism of Wnt signaling pathway activation. Int. Rev. cell Mol. Biol. 291 (2011), 21–71.
56. Kim, T.H., Kim, B.M., Mao, J., Rowan, S., Shivdasani, R.A., Endodermal Hedgehog signals modulate Notch pathway activity in the developing digestive tract mesenchyme. Development 138 (2011), 3225–3233.
57. Koliaraki, V., Pasparakis, M., Kollias, G., IKKbeta in intestinal mesenchymal cells promotes initiation of colitis-associated cancer. J. Exp. Med. 212 (2015), 2235–2251.
58. Koliaraki, V., Roulis, M., Kollias, G., Tpl2 regulates intestinal myofibroblast HGF release to suppress colitis-associated tumorigenesis. J. Clin. Investig. 122 (2012), 4231–4242.
59. Koltsova, E.K., Grivennikov, S.I., IMPlicating mesenchymal Imp1 in colitis-associated cancer. Mol. cancer Res.: MCR 13 (2015), 1452–1454.
60. Komuro, T., Fenestrations of the basal lamina of intestinal villi of the rat. Scanning and transmission electron microscopy. Cell tissue Res. 239 (1985), 183–188.
61. Kontoyiannis, D., Pasparakis, M., Pizarro, T.T., Cominelli, F., Kollias, G., Impaired on/off regulation of TNF biosynthesis in mice lacking TNF AU-rich elements: implications for joint and gut-associated immunopathologies. Immunity 10 (1999), 387–398.
62. Kosinski, C., Li, V.S., Chan, A.S., Zhang, J., Ho, C., Tsui, W.Y., Chan, T.L., Mifflin, R.C., Powell, D.W., Yuen, S.T., Leung, S.Y., Chen, X., Gene expression patterns of human colon tops and basal crypts and BMP antagonists as intestinal stem cell niche factors. Proc. Natl. Acad. Sci. USA 104 (2007), 15418–15423.
63. Kosinski, C., Stange, D.E., Xu, C., Chan, A.S., Ho, C., Yuen, S.T., Mifflin, R.C., Powell, D.W., Clevers, H., Leung, S.Y., Chen, X., Indian hedgehog regulates intestinal stem cell fate through epithelial-mesenchymal interactions during development. Gastroenterology 139 (2010), 893–903.
64. Kurahashi, M., Nakano, Y., Peri, L.E., Townsend, J.B., Ward, S.M., Sanders, K.M., A novel population of subepithelial platelet-derived growth factor receptor alpha-positive cells in the mouse and human colon. Am. J. Physiol. 304 (2013), G823–G834.
65. Labelle, M., Begum, S., Hynes, Richard, O., Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell 20 (2011), 576–590.
66. Lahar, N., Lei, N.Y., Wang, J., Jabaji, Z., Tung, S.C., Joshi, V., Lewis, M., Stelzner, M., Martín, M.G., Dunn, J.C.Y., Intestinal subepithelial myofibroblasts support in vitro and in vivo growth of human small intestinal epithelium. PLoS One, 6, 2011, e26898.
67. Le Guen, L., Marchal, S., Faure, S., de Santa Barbara, P., Mesenchymal-epithelial interactions during digestive tract development and epithelial stem cell regeneration. Cell. Mol. Life Sci., 2015.
68. Lei, N.Y., Jabaji, Z., Wang, J., Joshi, V.S., Brinkley, G.J., Khalil, H., Wang, F., Jaroszewicz, A., Pellegrini, M., Li, L., Lewis, M., Stelzner, M., Dunn, J.C.Y., Martín, M.G., Intestinal subepithelial myofibroblasts support the growth of intestinal epithelial stem cells. PLoS One, 9, 2014, e84651.
69. Li, X., Madison, B.B., Zacharias, W., Kolterud, A., States, D., Gumucio, D.L., Deconvoluting the intestine: molecular evidence for a major role of the mesenchyme in the modulation of signaling cross talk. Physiol. Genom. 29 (2007), 290–301.
70. Lotti, F., Jarrar, A.M., Pai, R.K., Hitomi, M., Lathia, J., Mace, A., Gantt, G.A. Jr., Sukhdeo, K., DeVecchio, J., Vasanji, A., Leahy, P., Hjelmeland, A.B., Kalady, M.F., Rich, J.N., Chemotherapy activates cancer-associated fibroblasts to maintain colorectal cancer-initiating cells by IL-17A. J. Exp. Med. 210 (2013), 2851–2872.
71. Madar, S., Goldstein, I., Rotter, V., 'Cancer associated fibroblasts’ – more than meets the eye. Trends Mol. Med. 19 (2013), 447–453.
72. Madison, B.B., Braunstein, K., Kuizon, E., Portman, K., Qiao, X.T., Gumucio, D.L., Epithelial hedgehog signals pattern the intestinal crypt-villus axis. Development 132 (2005), 279–289.
73. Manieri, N.A., Drylewicz, M.R., Miyoshi, H., Stappenbeck, T.S., Igf2bp1 is required for full induction of Ptgs2 mRNA in colonic mesenchymal stem cells in mice. Gastroenterology 143 (2012), 110–121 e110.
74. Mao, J., Kim, B.-M., Rajurkar, M., Shivdasani, R.A., McMahon, A.P., Hedgehog signaling controls mesenchymal growth in the developing mammalian digestive tract. Development 137 (2010), 1721–1729.
75. McKaig, B.C., McWilliams, D., Watson, S.A., Mahida, Y.R., Expression and regulation of tissue inhibitor of metalloproteinase-1 and matrix metalloproteinases by intestinal myofibroblasts in inflammatory bowel disease. Am. J. Pathol. 162 (2003), 1355–1360.
76. McLin, V.A., Henning, S.J., Jamrich, M., The role of the visceral mesoderm in the development of the gastrointestinal tract. Gastroenterology 136 (2009), 2074–2091.
77. Mifflin, R.C., Pinchuk, I.V., Saada, J.I., Powell, D.W., Intestinal myofibroblasts: targets for stem cell therapy. Am. J. Physiol. 300 (2011), G684–G696.
78. Mifflin, R.C., Saada, J.I., Di Mari, J.F., Adegboyega, P.A., Valentich, J.D., Powell, D.W., Regulation of COX-2 expression in human intestinal myofibroblasts: mechanisms of IL-1-mediated induction. Am. J. Physiol. 282 (2002), C824–C834.
79. Nemeth, M.J., Topol, L., Anderson, S.M., Yang, Y., Bodine, D.M., Wnt5a inhibits canonical Wnt signaling in hematopoietic stem cells and enhances repopulation. Proc. Natl. Acad. Sci. 104 (2007), 15436–15441.
80. Nik, A.M., Reyahi, A., Ponten, F., Carlsson, P., Foxf2 in intestinal fibroblasts reduces numbers of Lgr5(+) stem cells and adenoma formation by inhibiting Wnt signaling. Gastroenterology 144 (2013), 1001–1011.
81. Noah, T.K., Shroyer, N.F., Notch in the intestine: regulation of homeostasis and pathogenesis. Annu. Rev. Physiol. 75 (2013), 263–288.
82. Obermayr, F., Hotta, R., Enomoto, H., Young, H.M., Development and developmental disorders of the enteric nervous system. Nat. Rev. Gastroenterol. Hepatol. 10 (2013), 43–57.
83. Ohlund, D., Elyada, E., Tuveson, D., Fibroblast heterogeneity in the cancer wound. J. Exp. Med. 211 (2014), 1503–1523.
84. Okuno, T., Andoh, A., Bamba, S., Araki, Y., Fujiyama, Y., Fujiyama, M., Bamba, T., Interleukin-1beta and tumor necrosis factor-alpha induce chemokine and matrix metalloproteinase gene expression in human colonic subepithelial myofibroblasts. Scand. J. Gastroenterol. 37 (2002), 317–324.
85. Ormestad, M., Astorga, J., Landgren, H., Wang, T., Johansson, B.R., Miura, N., Carlsson, P., Foxf1 and Foxf2 control murine gut development by limiting mesenchymal Wnt signaling and promoting extracellular matrix production. Development 133 (2006), 833–843.
86. Ornitz, D.M., Itoh, N., The fibroblast growth factor signaling pathway. Wiley Interdiscip. Rev.: Dev. Biol. 4 (2015), 215–266.
87. Otte, J.M., Rosenberg, I.M., Podolsky, D.K., Intestinal myofibroblasts in innate immune responses of the intestine. Gastroenterology 124 (2003), 1866–1878.
88. Pallangyo, C.K., Ziegler, P.K., Greten, F.R., IKKbeta acts as a tumor suppressor in cancer-associated fibroblasts during intestinal tumorigenesis. J. Exp. Med. 212 (2015), 2253–2266.
89. Pinchuk, I.V., Beswick, E.J., Saada, J.I., Boya, G., Schmitt, D., Raju, G.S., Brenmoehl, J., Rogler, G., Reyes, V.E., Powell, D.W., Human colonic myofibroblasts promote expansion of CD4+ CD25high Foxp3+ regulatory T cells. Gastroenterology 140 (2011), 2019–2030.
90. Pinchuk, I.V., Mifflin, R.C., Saada, J.I., Powell, D.W., Intestinal mesenchymal cells. Curr. Gastroenterol. Rep. 12 (2010), 310–318.
91. Pinchuk, I.V., Saada, J.I., Beswick, E.J., Boya, G., Qiu, S.M., Mifflin, R.C., Raju, G.S., Reyes, V.E., Powell, D.W., PD-1 ligand expression by human colonic myofibroblasts/fibroblasts regulates CD4+ T-cell activity. Gastroenterology 135 (2008), 1228–1237 e1222.
92. Powell, D.W., Adegboyega, P.A., Di Mari, J.F., Mifflin, R.C., Epithelial cells and their neighbors I. Role of intestinal myofibroblasts in development, repair, and cancer. Am. J. Physiol. 289 (2005), G2–G7.
93. Powell, D.W., Mifflin, R.C., Valentich, J.D., Crowe, S.E., Saada, J.I., West, A.B., Myofibroblasts. II. Intestinal subepithelial myofibroblasts. Am. J. Physiol. 277 (1999), C183–C201.
94. Powell, D.W., Pinchuk, I.V., Saada, J.I., Chen, X., Mifflin, R.C., Mesenchymal cells of the intestinal lamina propria. Annu. Rev. Physiol. 73 (2011), 213–237.
95. Quante, M., Varga, J., Wang, T.C., Greten, F.R., The gastrointestinal tumor microenvironment. Gastroenterology 145 (2013), 63–78.
96. Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S., Medzhitov, R., Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell 118 (2004), 229–241.
97. Ramalho-Santos, M., Melton, D.A., McMahon, A.P., Hedgehog signals regulate multiple aspects of gastrointestinal development. Development 127 (2000), 2763–2772.
98. Rieder, F., Fiocchi, C., Intestinal fibrosis in IBD—a dynamic, multifactorial process. Nat. Rev. Gastroenterol. Hepatol. 6 (2009), 228–235.
99. Rieder, F., Fiocchi, C., Mechanisms of tissue remodeling in inflammatory bowel disease. Dig. Dis. 31 (2013), 186–193.
100. Rieder, F., Kessler, S.P., West, G.A., Bhilocha, S., de la Motte, C., Sadler, T.M., Gopalan, B., Stylianou, E., Fiocchi, C., Inflammation-induced endothelial-to-mesenchymal transition: a novel mechanism of intestinal fibrosis. Am. J. Pathol. 179 (2011), 2660–2673.
101. Rinkevich, Y., Mori, T., Sahoo, D., Xu, P.X., Bermingham, J.R. Jr., Weissman, I.L., Identification and prospective isolation of a mesothelial precursor lineage giving rise to smooth muscle cells and fibroblasts for mammalian internal organs, and their vasculature. Nat. cell Biol. 14 (2012), 1251–1260.
102. Roulis, M., Armaka, M., Manoloukos, M., Apostolaki, M., Kollias, G., Intestinal epithelial cells as producers but not targets of chronic TNF suffice to cause murine Crohn-like pathology. Proc. Natl. Acad. Sci. USA 108 (2011), 5396–5401.
103. Roulis, M., Nikolaou, C., Kotsaki, E., Kaffe, E., Karagianni, N., Koliaraki, V., Salpea, K., Ragoussis, J., Aidinis, V., Martini, E., Becker, C., Herschman, H.R., Vetrano, S., Danese, S., Kollias, G., Intestinal myofibroblast-specific Tpl2-Cox-2-PGE2 pathway links innate sensing to epithelial homeostasis. Proc. Natl. Acad. Sci. USA 111 (2014), E4658–E4667.
104. Saada, J.I., Pinchuk, I.V., Barrera, C.A., Adegboyega, P.A., Suarez, G., Mifflin, R.C., Di Mari, J.F., Reyes, V.E., Powell, D.W., Subepithelial myofibroblasts are novel nonprofessional APCs in the human colonic mucosa. J. Immunol. 177 (2006), 5968–5979.
105. San Roman, Adrianna K., Jayewickreme, Chenura, D., Murtaugh, L.C., Shivdasani, Ramesh, A., Wnt secretion from epithelial cells and subepithelial myofibroblasts is not required in the mouse intestinal stem cell niche in vivo. Stem Cell Rep. 2 (2014), 127–134.
106. Sancho, R., Cremona, C.A., Behrens, A., 2015. Stem cell and progenitor fate in the mammalian intestine: Notch and lateral Inhibition in Homeostasis and Disease.
107. Sato, T., van Es, J.H., Snippert, H.J., Stange, D.E., Vries, R.G., van den Born, M., Barker, N., Shroyer, N.F., van de Wetering, M., Clevers, H., Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469 (2011), 415–418.
108. Sato, T., Vries, R.G., Snippert, H.J., van de Wetering, M., Barker, N., Stange, D.E., van Es, J.H., Abo, A., Kujala, P., Peters, P.J., Clevers, H., Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459 (2009), 262–265.
109. Scharl, M., Huber, N., Lang, S., Furst, A., Jehle, E., Rogler, G., Hallmarks of epithelial to mesenchymal transition are detectable in Crohn's disease associated intestinal fibrosis. Clin. Transl. Med., 4, 2015, 1.
110. Shaker, A., Swietlicki, E.A., Wang, L., Jiang, S., Onal, B., Bala, S., DeSchryver, K., Newberry, R., Levin, M.S., Rubin, D.C., Epimorphin deletion protects mice from inflammation-induced colon carcinogenesis and alters stem cell niche myofibroblast secretion. J. Clin. Investig. 120 (2010), 2081–2093.
111. Shih, D.Q., Zheng, L., Zhang, X., Zhang, H., Kanazawa, Y., Ichikawa, R., Wallace, K.L., Chen, J., Pothoulakis, C., Koon, H.W., Targan, S.R., Inhibition of a novel fibrogenic factor Tl1a reverses established colonic fibrosis. Mucosal Immunol. 7 (2014), 1492–1503.
112. Spence, J.R., Lauf, R., Shroyer, N.F., Vertebrate intestinal endoderm development. Dev. Dyn. 240 (2011), 501–520.
113. Stanisavljevic, J., Loubat-Casanovas, J., Herrera, M., Luque, T., Pena, R., Lluch, A., Albanell, J., Bonilla, F., Rovira, A., Pena, C., Navajas, D., Rojo, F., Garcia de Herreros, A., Baulida, J., Snail1-expressing fibroblasts in the tumor microenvironment display mechanical properties that support metastasis. Cancer Res. 75 (2015), 284–295.
114. Straussman, R., Morikawa, T., Shee, K., Barzily-Rokni, M., Qian, Z.R., Du, J., Davis, A., Mongare, M.M., Gould, J., Frederick, D.T., Cooper, Z.A., Chapman, P.B., Solit, D.B., Ribas, A., Lo, R.S., Flaherty, K.T., Ogino, S., Wargo, J.A., Golub, T.R., Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature 487 (2012), 500–504.
115. Sugimoto, H., Mundel, T.M., Kieran, M.W., Kalluri, R., Identification of fibroblast heterogeneity in the tumor microenvironment. Cancer Biol. Ther. 5 (2006), 1640–1646.
116. Swietlicki, E.A., Bala, S., Lu, J., Shaker, A., Kularatna, G., Levin, M.S., Rubin, D.C., Epimorphin deletion inhibits polyposis in the Apcmin/+ mouse model of colon carcinogenesis via decreased myofibroblast HGF secretion. Am. J. Physiol. 305 (2013), G564–G572.
117. Tan, D.W., Barker, N., Intestinal stem cells and their defining niche. Curr. Top. Dev. Biol. 107 (2014), 77–107.
118. Theiss, A.L., Simmons, J.G., Jobin, C., Lund, P.K., Tumor necrosis factor (TNF) alpha increases collagen accumulation and proliferation in intestinal myofibroblasts via TNF receptor 2. J. Biol. Chem. 280 (2005), 36099–36109.
119. Tomasek, J.J., Gabbiani, G., Hinz, B., Chaponnier, C., Brown, R.A., Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat. Rev. Mol. Cell Biol. 3 (2002), 349–363.
120. Toyoda, H., Ina, K., Kitamura, H., Tsuda, T., Shimada, T., Organization of the lamina propria mucosae of rat intestinal mucosa, with special reference to the subepithelial connective tissue. Acta Anat. 158 (1997), 172–184.
121. G.R., van den Brink, 2007. Hedgehog Signaling in Development and Homeostasis of the Gastrointestinal Tract.
122. VanDussen, K.L., Carulli, A.J., Keeley, T.M., Patel, S.R., Puthoff, B.J., Magness, S.T., Tran, I.T., Maillard, I., Siebel, C., Kolterud, A., Grosse, A.S., Gumucio, D.L., Ernst, S.A., Tsai, Y.H., Dempsey, P.J., Samuelson, L.C., Notch signaling modulates proliferation and differentiation of intestinal crypt base columnar stem cells. Development 139 (2012), 488–497.
123. Vermeulen, L., De Sousa, E.M.F., van der Heijden, M., Cameron, K., de Jong, J.H., Borovski, T., Tuynman, J.B., Todaro, M., Merz, C., Rodermond, H., Sprick, M.R., Kemper, K., Richel, D.J., Stassi, G., Medema, J.P., Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat. cell Biol. 12 (2010), 468–476.
124. Vicente-Suarez, I., Larange, A., Reardon, C., Matho, M., Feau, S., Chodaczek, G., Park, Y., Obata, Y., Gold, R., Wang-Zhu, Y., Lena, C., Zajonc, D.M., Schoenberger, S.P., Kronenberg, M., Cheroutre, H., Unique lamina propria stromal cells imprint the functional phenotype of mucosal dendritic cells. Mucosal Immunol. 8 (2015), 141–151.
125. Walton, K.D., Kolterud, A., Czerwinski, M.J., Bell, M.J., Prakash, A., Kushwaha, J., Grosse, A.S., Schnell, S., Gumucio, D.L., Hedgehog-responsive mesenchymal clusters direct patterning and emergence of intestinal villi. Proc. Natl. Acad. Sci. USA 109 (2012), 15817–15822.
126. Walton, K.L., Holt, L., Sartor, R.B., Lipopolysaccharide activates innate immune responses in murine intestinal myofibroblasts through multiple signaling pathways. Am. J. Physiol. 296 (2009), G601–G611.
127. Wilm, B., Ipenberg, A., Hastie, N.D., Burch, J.B.E., Bader, D.M., The serosal mesothelium is a major source of smooth muscle cells of the gut vasculature. Development 132 (2005), 5317–5328.
128. Wirth, A., Benyo, Z., Lukasova, M., Leutgeb, B., Wettschureck, N., Gorbey, S., Orsy, P., Horvath, B., Maser-Gluth, C., Greiner, E., Lemmer, B., Schutz, G., Gutkind, J.S., Offermanns, S., G12-G13-LARG-mediated signaling in vascular smooth muscle is required for salt-induced hypertension. Nat. Med. 14 (2008), 64–68.
129. Worthley, D.L., Giraud, A.S., Wang, T.C., Stromal fibroblasts in digestive cancer. Cancer Microenviron. 3 (2010), 117–125.
130. Xin, H.B., Deng, K.Y., Rishniw, M., Ji, G., Kotlikoff, M.I., Smooth muscle expression of Cre recombinase and eGFP in transgenic mice. Physiol. Genom. 10 (2002), 211–215.
131. Zhang, X., Stappenbeck, T.S., White, A.C., Lavine, K.J., Gordon, J.I., Ornitz, D.M., Reciprocal epithelial-mesenchymal FGF signaling is required for cecal development. Development 133 (2006), 173–180.