Smad3 knockout mice exhibit impaired intestinal mucosal healing

Laboratory Investigation

Volumn 88, Issue 10, 2008, Pages 1101-1109

  Owen, Cheri R ^a   Yuan, Lisi ^a   Basson, Marc D ^a,b  

^a WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Cell migration; Inflammatory bowel disease; Smad3; TGF ; Ulcer; Wound healing

Indexed keywords

ACETIC ACID; CELL NUCLEUS ANTIGEN; FOCAL ADHESION KINASE; MITOGEN ACTIVATED PROTEIN KINASE 3; SMAD3 PROTEIN; TRANSFORMING GROWTH FACTOR BETA;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; CELL DEATH; CELL MIGRATION; CONTROLLED STUDY; FEMALE; IMMUNOREACTIVITY; INTESTINE EPITHELIUM; INTESTINE ISCHEMIA; INTESTINE MUCOSA; INTESTINE ULCER; KNOCKOUT MOUSE; MALE; MOUSE; MOUSE STRAIN; NICK END LABELING; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; SIGNAL TRANSDUCTION; WILD TYPE; WOUND HEALING IMPAIRMENT;

ANIMALS; DISEASE MODELS, ANIMAL; FEMALE; INFLAMMATORY BOWEL DISEASES; INTESTINAL MUCOSA; JEJUNUM; MALE; MICE; MICE, KNOCKOUT; SIGNAL TRANSDUCTION; SMAD3 PROTEIN; TRANSFORMING GROWTH FACTOR BETA; WOUND HEALING;

EID: 52649124170     PISSN: 00236837     EISSN: 15300307     Source Type: Journal    
DOI: 10.1038/labinvest.2008.77     Document Type: Article

References (65)

1. Okamoto R, Watanabe M. Cellular and molecular mechanisms of the epithelial repair in IBD. Dig Dis Sci 2005;50(Suppl 1):S34-S38.
2. Basson MD, Rashid Z, Turowski GA, et al. Restitution at the cellular level: regulation of the migrating phenotype. Yale J Biol Med 1996;69:119-129.
3. Dignass AU, Podolsky DK. Interleukin 2 modulates intestinal epithelial cell function in vitro. Exp Cell Res 1996;225:422-429.
4. Sasaki H, Hirai K, Yamamoto H, et al. HST-1/FGF-4 plays a critical role in crypt cell survival and facilitates epithelial cell restitution and proliferation. Oncogene 2004;23:3681-3688.
5. Ramsanahie AP, Perez A, Duensing AU, et al. Glucagon-like peptide 2 enhances intestinal epithelial restitution. J Surg Res 2002;107:44-49.
6. Nishimura S, Takahashi M, Ota S, et al. Hepatocyte growth factor accelerates restitution of intestinal epithelial cells. J Gastroenterol 1998;33:172-178.
7. Goke MN, Schneider M, Beil W, et al. Differential glucocorticoid effects on repair mechanisms and NF-kappaB activity in the intestinal epithelium. Regul Pept 2002;105:203-214.
8. Bascom CC, Wolfshohl JR, Coffey Jr RJ, et al. Complex regulation of transforming growth factor beta 1, beta 2, and beta 3 mRNA expression in mouse fibroblasts and keratinocytes by transforming growth factors beta 1 and beta 2. Mol Cell Biol 1989;9:5508-5515.
9. Massague J. How cells read TGF-beta signals. Nat Rev Mol Cell Biol 2000;1:169-178.
10. Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 2003;113:685-700.
11. Chai J, Baatar D, Tarnawski A. Serum response factor promotes re-epithelialization and muscular structure restoration during gastric ulcer healing. Gastroenterology 2004;126:1809-1818.
12. Leeb SN, Vogl D, Gunckel M, et al. Reduced migration of fibroblasts in inflammatory bowel disease: role of inflammatory mediators and focal adhesion kinase. Gastroenterology 2003;125:1341-1354.
13. Corredor J, Yan F, Shen CC, et al. Tumor necrosis factor regulates intestinal epithelial cell migration by receptor-dependent mechanisms. Am J Physiol Cell Physiol 2003;284:C953-C961.
14. Tarnawski AS, Pai R, Wang H, et al. Translocation of MAP (Erk-1 and -2) kinases to cell nuclei and activation of c-fos gene during healing of experimental gastric ulcers. J Physiol Pharmacol 1998;49:479-488.
15. Feng XH, Derynck R. Specificity and versatility in tgf-beta signaling through Smads. Annu Rev Cell Dev Biol 2005;21:659-693.
16. Tarnawski A. Molecular mechanisms of ulcer healing. Drug News Perspect 2000;13:158-168.
17. Yang X, Letterio JJ, Lechleider RJ, et al. Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-beta. EMBO J 1999;18:1280-1291.
18. Tarnawski A, Hollander D, Krause WJ, et al. 'Healed' experimental gastric ulcers remain histologically and ultrastructurally abnormal. J Clin Gastroenterol 1990;12(Suppl 1):S139-S147.
19. Waseem NH, Lane DP. Monoclonal antibody analysis of the proliferating cell nuclear antigen (PCNA). Structural conservation and the detection of a nucleolar form. J Cell Sci 1990;96(Part 1):121-129.
20. Pai R, Ohta M, Itani RM, et al. Induction of mitogen-activated protein kinase signal transduction pathway during gastric ulcer healing in rats. Gastroenterology 1998;114:706-713.
21. Wallace JL, Dicay M, McKnight W, et al. Hydrogen sulfide enhances ulcer healing in rats. FASEB J 2007;21:4070-4076.
22. Ohno T, Hattori Y, Komine R, et al. Roles of calcitonin gene-related peptide in maintenance of gastric mucosal integrity and in enhancement of ulcer healing and angiogenesis. Gastroenterology 2008;134:215-225.
23. Kong J, Zhang Z, Musch MW, et al. Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier. Am J Physiol Gastrointest Liver Physiol 2008;294:G208-G216.
24. Dennler S, Goumans MJ, ten Dijke P. Transforming growth factor beta signal transduction. J Leukoc Biol 2002;71:731-740.
25. Arany PR, Flanders KC, Kobayashi T, et al. Smad3 deficiency alters key structural elements of the extracellular matrix and mechanotransduction of wound closure. Proc Natl Acad Sci USA 2006;103:9250-9255.
26. Wong WM, Playford RJ, Wright NA. Peptide gene expression in gastrointestinal mucosal ulceration: ordered sequence or redundancy? Gut 2000;46:286-292.
27. Tarnawski AS, Jones MK. The role of epidermal growth factor (EGF) and its receptor in mucosal protection, adaptation to injury, and ulcer healing: involvement of EGF-R signal transduction pathways. J Clin Gastroenterol 1998;27(Suppl 1):S12-S20.
28. Kader HA, Tchernev VT, Satyaraj E, et al. Protein microarray analysis of disease activity in pediatric inflammatory bowel disease demonstrates elevated serum PLGF, IL-7, TGF-beta1, and IL-12p40 levels in Crohn's disease and ulcerative colitis patients in remission versus active disease. Am J Gastroenterol 2005;100:414-423.
29. Del Zotto B, Mumolo G, Pronio AM, et al. TGF-beta1 production in inflammatory bowel disease: differing production patterns in Crohn's disease and ulcerative colitis. Clin Exp Immunol 2003;134:120-126.
30. Kulkarni AB, Huh CG, Becker D, et al. Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death. Proc Natl Acad Sci USA 1993;90:770-774.
31. Shull MM, Ormsby I, Kier AB, et al. Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature 1992;359:693-699.
32. Kaartinen V, Voncken JW, Shuler C, et al. Abnormal lung development and cleft palate in mice lacking TGF-beta 3 indicates defects of epithelial-mesenchymal interaction. Nat Genet 1995;11:415-421.
33. Proetzel G, Pawlowski SA, Wiles MV, et al. Transforming growth factor-beta 3 is required for secondary palate fusion. Nat Genet 1995;11:409-414.
34. Sanford LP, Ormsby I, Gittenberger-de Groot AC, et al. TGFbeta2 knockout mice have multiple developmental defects that are non-overlapping with other TGFbeta knockout phenotypes. Development 1997;124:2659-2670.
35. Souza RF, Garrigue-Antar L, Lei J, et al. Alterations of transforming growth factor-beta 1 receptor type II occur in ulcerative colitis-associated carcinomas, sporadic colorectal neoplasms, and esophageal carcinomas, but not in gastric neoplasms. Hum Cell 1996;9:229-236.
36. Souza RF, Lei J, Yin J, et al. A transforming growth factor beta 1 receptor type II mutation in ulcerative colitis-associated neoplasms. Gastroenterology 1997;112:40-45.
37. Hahm KB, Im YH, Parks TW, et al. Loss of transforming growth factor beta signalling in the intestine contributes to tissue injury in inflammatory bowel disease. Gut 2001;49:190-198.
38. Ciacci C, Lind SE, Podolsky DK. Transforming growth factor beta regulation of migration in wounded rat intestinal epithelial monolayers. Gastroenterology 1993;105:93-101.
39. Basson MD, Modlin IM, Flynn SD, et al. Independent modulation of enterocyte migration and proliferation by growth factors, matrix proteins, and pharmacologic agents in an in vitro model of mucosal healing. Surgery 1992;112:299-307; discussion 307-298.
40. Reynolds LE, Conti FJ, Lucas M, et al. Accelerated re-epithelialization in beta3-integrin-deficient- mice is associated with enhanced TGF-beta1 signaling. Nat Med 2005;11:167-174.
41. Beck PL, Rosenberg IM, Xavier RJ, et al. Transforming growth factor-beta mediates intestinal healing and susceptibility to injury in vitro and in vivo through epithelial cells. Am J Pathol 2003;162:597-608.
42. Wang A, Ziyadeh FN, Lee EY, et al. Interference with TGF-beta signaling by Smad3-knockout in mice limits diabetic glomerulosclerosis without affecting albuminuria. Am J Physiol Renal Physiol 2007;293:F1657-F1665.
43. Zanninelli G, Vetuschi A, Sferra R, et al. Smad3 knock-out mice as a useful model to study intestinal fibrogenesis. World J Gastroenterol 2006;12:1211-1218.
44. Snape Jr WJ, Williams R, Hyman PE. Defect in colonic smooth muscle contraction in patients with ulcerative colitis. Am J Physiol 1991;261(6 Part 1):G987-G991.
45. Snape Jr WJ, Kao HW. Role of inflammatory mediators in colonic smooth muscle function in ulcerative colitis. Dig Dis Sci 1988;33(3 Suppl):65S-70S.
46. Sethi AK, Sarna SK. Colonic motor activity in acute colitis in conscious dogs. Gastroenterology 1991;100:954-963.
47. Wang Y, Moges H, Bharucha Y, et al. Smad3 null mice display more rapid wound closure and reduced scar formation after a stab wound to the cerebral cortex. Exp Neurol 2007;203:168-184.
48. Falanga V, Schrayer D, Cha J, et al. Full-thickness wounding of the mouse tail as a model for delayed wound healing: accelerated wound closure in Smad3 knock-out mice. Wound Repair Regen 2004;12:320-326.
49. Tokumasa A, Katsuno T, Tanaga TS, et al. Reduction of Smad3 accelerates re-epithelialization in a murine model of colitis. Biochem Biophys Res Commun 2004;317:377-383.
50. Amendt C, Mann A, Schirmacher P, et al. Resistance of keratinocytes to TGFβ-mediated growth restriction and apoptosis induction accelerates re-epithelialization in skin wounds. J Cell Sci 2002;115(Part 10):2189-2198.
51. Grossi L, McHugh K, Collins SM. On the specificity of altered muscle function in experimental colitis in rats. Gastroenterology 1993;104:1049-1056.
52. Zhang J, Owen CR, Sanders MA, et al. The motogenic effects of cyclic mechanical strain on intestinal epithelial monolayer wound closure are matrix dependent. Gastroenterology 2006;131:1179-1189.
53. Liu YW, Sanders MA, Basson MD. Human Caco-2 intestinal epithelial motility is associated with tyrosine kinase and cytoskeletal focal adhesion kinase signals. J Surg Res 1998;77:112-118.
54. Tilghman RW, Slack-Davis JK, Sergina N, et al. Focal adhesion kinase is required for the spatial organization of the leading edge in migrating cells. J Cell Sci 2005;118(Part 12):2613-2623.
55. Yu CF, Sanders MA, Basson MD. Human caco-2 motility redistributes FAK and paxillin and activates p38 MAPK in a matrix-dependent manner. Am J Physiol Gastrointest Liver Physiol 2000;278:G952-G966.
56. Jiang X, Jacamo R, Zhukova E, et al. RNA interference reveals a differential role of FAK and Pyk2 in cell migration, leading edge formation and increase in focal adhesions induced by LPA in intestinal epithelial cells. J Cell Physiol 2006;207:816-828.
57. Basson MD, Sanders MA, Gomez R, et al. Focal adhesion kinase protein levels in gut epithelial motility. Am J Physiol Gastrointest Liver Physiol 2006;291:G491-G499.
58. Essayem S, Kovacic-Milivojevic B, Baumbusch C, et al. Hair cycle and wound healing in mice with a keratinocyte-restricted deletion of FAK. Oncogene 2006;25:1081-1089.
59. Garat C, Arend WP. Intracellular IL-1Ra type 1 inhibits IL-1-induced IL-6 and IL-8 production in Caco-2 intestinal epithelial cells through inhibition of p38 mitogen-activated protein kinase and NF-kappaB pathways. Cytokine 2003;23:31-40.
60. Waetzig GH, Seegert D, Rosenstiel P, et al. p38 Mitogen-activated protein kinase is activated and linked to TNF-alpha signaling in inflammatory bowel disease. J Immunol 2002;168:5342-5351.
61. Matsubayashi Y, Ebisuya M, Honjoh S, et al. ERK activation propagates in epithelial cell sheets and regulates their migration during wound healing. Curr Biol 2004;14:731-735.
62. Joslin EJ, Opresko LK, Wells A, et al. EGF-receptor-mediated mammary epithelial cell migration is driven by sustained ERK signaling from autocrine stimulation. J Cell Sci 2007;120(Part 20):3688-3699.
63. Arany PR, Rane SG, Roberts AB. Smad3 deficiency inhibits v-ras-induced transformation by suppression of JNK MAPK signaling and increased farnesyl transferase inhibition. Oncogene 2008;27:2507-2512.
64. Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 2003;425:577-584.
65. Leivonen SK, Hakkinen L, Liu D, et al. Smad3 and extracellular signal-regulated kinase 1/2 coordinately mediate transforming growth factor-beta-induced expression of connective tissue growth factor in human fibroblasts. J Invest Dermatol 2005;124:1162-1169.