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Serum Basic Fibroblast Growth Factor in Pediatric Crohn's Disease (Implications for Wound Healing)

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Abstract

Basic fibroblast growth factor is aheparin-binding protein known to stimulate angiogenesisand promote wound healing in tissues. Since Crohn'sdisease is characterized in part by submucosal vascularproliferation, we sought to determine whether serum basicfibroblast growth factor is elevated in children withCrohn's disease and whether serum levels reflect diseaseactivity. Sera were obtained from 64 children with Crohn's disease, 44 children with ulcerativecolitis, 20 children with functional abdominal pain, and29 from children with documented inflammatory diseaseevaluated in our gastroenterology program. Disease activity indices and clinical data weregathered prospectively for the inflammatory boweldisease patients. Serum basic fibroblast growth factorlevels were measured by enzyme-linked immunosorbentassay. Although the mean basic fibroblast growthfactor level did not significantly differ betweenchildren with Crohn's disease and other conditions,there was a strong (r = 0.53, P < 0.001) correlationbetween basic fibroblast growth factor level and diseaseactivity. The relationship of basic fibroblast growthfactor with disease activity persisted even afteradjusting for other covariates (including age, sex,hematocrit, albumin, and sedimentation rate) in amultivariate linear regression model. There was also astatistically significant, although less strongcorrelation (r = 0.33, P = 0.03) between basicfibroblast growth factor level and disease activity in ulcerativecolitis. While basic fibroblast growth factor is not aspecific marker for Crohn's disease, serum levelsreflect disease activity. Therefore, basic fibroblast growth factor release may be important inmediating the angiogenesis and wound healing seen inCrohn's disease.

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REFERENCES

  1. Sartor RB: Current concepts in the etiology and pathogenesis of ulcerative colitis and Crohn's disease. Gastroenterol Clin North Am 24:475–507, 1995

    Google Scholar 

  2. Yang H, Rotter JI: Genetic aspects of idiopathic inflammatory bowel disease. In Inflammatory Bowel Disease, 4th ed. JB Kirsner, RG Shorter. (eds). Baltimore, Williams and Wilkins, 1995, pp 301–334

    Google Scholar 

  3. Schreiber S, Raedler A, Stenson WF, McDermott RP: The role of the mucosal immune system in inflammatory bowel disease. Gastroenterol Clin North Am 21:451–502, 1992

    Google Scholar 

  4. Wakefield AJ, Dhillon AP, Rowles PM, Sawyer AM, Pittilo RM, Lewis AM, Pounder RE: Pathogenesis of Crohn's disease: Multifocal gastrointestinal infarction. Lancet 2:1057–1062, 1989

    Google Scholar 

  5. Schweigerer L, Fotsis T: Angiogenesis and angiogenesis inhibitors in pediatric diseases. Eur J Pediatr 151:472–476, 1992

    Google Scholar 

  6. Rifkin DB, Moscatelli D: Recent developments in the cell biology of basic fibroblast growth factor. J Cell Biol 106:1–6, 1989

    Google Scholar 

  7. Slavin A: Fibroblast growth factors: at the heart of angiogenesis. Cell Biol Int 19:431–444, 1995

    Google Scholar 

  8. Friese RE, Maciag T: Molecular mechanisms of angiogenesis: Fibroblast growth factor signal transduction. FASEB J 9:919–925, 1995 (review)

    Google Scholar 

  9. Folkman J: Clinical application of research on angiogenesis. N Engl J Med 333:1757–1763, 1995

    Google Scholar 

  10. New BA, Yeoman LC: Identification of basic fibroblast growth factor and sensitivity and receptor and ligand expression in human colon tumor cell lines. J Cell Physiol 150:320–326, 1992

    Google Scholar 

  11. Nice EC, Fabri L, Whitehead RH, James R, Simpson RJ, Burgess AW: The major colonic cell mitogen extractable from colonic mucosa is an N-terminally extended form of basic fibroblast growth factor. J Biol Chem 22:14425–14430, 1991

    Google Scholar 

  12. Cordon-Cardo C, Vlodaavsky I, Haimovitz-Friedman A, Hicklin D, Fuks Z: Expression of basic fibroblast growth factor in human tissues. Lab Invest 63:832–840, 1990

    Google Scholar 

  13. Schulze-Orloff K, Risau W, Vollmer E, Sorg C: In situ detection of basic fibroblast growth factor by highly specific antibodies. Am J Pathol 137:85–92, 1990

    Google Scholar 

  14. Dignass AU, Tsukenawa S, Podolsky DK: Fibroblast growth factors modulate intestinal epithelial cell growth and migration. Gastroenterology 106:1254–1262, 1994

    Google Scholar 

  15. Szabo S, Folkman J, Vattay P, Morales RE, Pinkus G, Kato K: Accelerated healing of duodenal ulcers by oral administration of a mutein of basic fibroblast growth factor in rats. Gastroenterology 106:1106–1111, 1994

    Google Scholar 

  16. D'Amore PA, Brown RH, Ku PT, Hoffman EP, Watanabe H, Arahata K, Ishihara T, Folkman J: Elevated serum basic fibroblast growth factor in the serum of patients with Duchenne muscular dystrophy. Ann Neurol 35:362–365, 1994

    Google Scholar 

  17. Hyams JS, Ferry GD, Mandel FS, Gryboski JD, Kibort PM, Kirschner BS, Griffiths AM, Katz AJ, Granel RJ, Boyle JT, Michener WM, Levy JS, Lesser ML: Development and validation of a pediatric Crohn's disease activity index. J Pediatr Gastroenterol Nutr 12:439–447, 1991

    Google Scholar 

  18. Hyams JS, Fitzgerald JE, Treem WR, Wyzga N, Kreutzer DL: Relationship of functional and antigenic interleukin-6 to disease activity in inflammatory bowel disease. Gastroenterology 104:1285–92, 1993

    Google Scholar 

  19. Kozarek RA, Patterson DJ, Gelfand MD, Botoman VA, Ball TJ, Wilske KR: Methotrexate induces clinical and histologic remission in patients with refractory inflammatory bowel disease. Ann Intern Med 110:353–356, 1989

    Google Scholar 

  20. Miller RG: Simultaneous Statistical Inference, 2nd ed. New York: Springer-Verlag, 1981, pp 67–73

    Google Scholar 

  21. Hamilton LC: Regression with Graphics: A Second Course in Applied Statistics. Belmont, California; Duxbury Press, 1992, pp 163–174

    Google Scholar 

  22. Bross DA, Leichtner AM, Zurakowski D, Law T, Bousvaros A: Elevation of serum interleukin-6 but not soluble interleukin-2 receptor in children with Crohn's disease. J Pediatr Gastroenterol Nutr 23:164–171, 1996

    Google Scholar 

  23. Olwin BB, Arthur K, Hannon K, Hein P, McFall A, Riley B, Szebenyi G, Zhaohui Zhou, Zuber ME, Rapraeger AC, Fallon JF, Kudla AJ: Role of FGF's in skeletal muscle and limb development. Mol reprod dev 39:90–101, 1994

    Google Scholar 

  24. Chua CC, Chua BH, Zhao ZY, Krebs C, Diglio C, Perrin E: Effect of growth factors on collagen metabolism in cultured human heart fibroblasts. Connect Tissue Res 26:271–282, 1991

    Google Scholar 

  25. Kennedy SH, Qin H, Lin L, Tan EM: Basic fibroblast growth factor regulates type I collagen and collagenase gene expression in human smooth muscle cells. Am J Pathol 146:764–771, 1995

    Google Scholar 

  26. Savage MP, Hart CE, Riley BB, Sasse J, Olwin BB, Fallon JF: Distribution of FGF-2 suggests it has a role in chick limb bud growth. Dev Dyn 198:159–170, 1993

    Google Scholar 

  27. Rutland P, Pulleyn LJ, Reardon W, Baraitser M, Hayward R, Jones B, Malcolm S, Winter RM, Oldridge M, Slaney SF, Poole MD, Wilkie AO: Identical mutations in the FGFR2 gene cause both Pfeiffer and Crouzon syndrome phenotypes. Nature Genet 9:173–176, 1995

    Google Scholar 

  28. Reidy MA: Neointimal proliferation: The role of basic FGF on vascular smooth muscle proliferation. Thromb Haemost 70:172–176, 1993

    Google Scholar 

  29. Mazue G, Bertolero F, Jacob C, Sarminetos P, Ronrucci R: Preclinical and clinical studies with recombinant human basic fibroblast growth factor. Ann NY Acad Sci 638:329–340, 1991

    Google Scholar 

  30. Davidson JM, Broadley KN: Manipulation of the wound-healing process with basic fibroblast growth factor. Ann NY Acad Sci 638:306–315, 1991

    Google Scholar 

  31. Duensing S, Atzpodien J: Increased intracellular and plasma levels of basic fibroblast growth factor in B-cell chronic lymphocytic leukemia. Blood 85:1978–1980, 1995

    Google Scholar 

  32. Nguyen M, Watanabe H, Budson AE, Richie JP, Hayes DF, Folkman J: Elevated levels of an angiogenic peptide, basic fibroblast growth factor, in the urine of patients with a wide spectrum of cancers. J Nat Cancer Inst 86:356–361, 1994

    Google Scholar 

  33. Folkman J, Szabo S, Stovroff M, McNeil P, Li M, Shing Y: Duodenal ulcer: Discovery of a new mechanism and development of angiogenic therapy that accelerates healing. Ann Surg 214:414–427, 1991

    Google Scholar 

  34. Proujansky R, Carpenter AB: Soluble interleukin-2 receptor as a marker of lymphocyte activation in childhood Crohn's disease. J Pediatr Gastroenterol Nutr 13:277–284, 1991

    Google Scholar 

  35. Gilmour HM: Crohn's disease. In Gastrointestinal and Oesophageal Pathology. R Whitehead (ed). Edinburgh, Churchill Livingstone, 1989, pp 458–467

    Google Scholar 

  36. Dvorak HF, Brown LF, Detmar M, Dvorak AM: Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am J Pathol 146:1030–1039, 1995

    Google Scholar 

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Authors
  1. Athos Bousvaros
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  2. David Zurakowski
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  3. Steven J. Fishman
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  4. Karen Keough
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  5. Terry Law
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  6. Christina Sun
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  7. Alan M. Leichtner
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Bousvaros, A., Zurakowski, D., Fishman, S.J. et al. Serum Basic Fibroblast Growth Factor in Pediatric Crohn's Disease (Implications for Wound Healing). Dig Dis Sci 42, 378–386 (1997). https://doi.org/10.1023/A:1018882322566

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