Journal of Gastroenterology

, Volume 31, Issue 3, pp 353–360 | Cite as

Growth factor mRNA expression in normal colorectal mucosa and in uninvolved mucosa from ulcerative colitis patients

  • Aktaruzzaman Chowdhury
  • Ryo Fukuda
  • Shiro Fukumoto
Alimentary Tract


This study was carried out to investigate the expression of various growth factors (GFs) involved in mucosal healing and thereby to clarify whether there are potential differences in the expression of GFs between normal colonic mucosa and the uninvolved mucosa of ulcerative colitis (UC). GF mRNA was investigated by reverse transcription polymerase chain reaction in colorectal biopsies from 20 normal controls and 15 UC patients. The positive rates (%) for mRNA expression for normal/UC were: epidermal growth factor (EGF) 65/53, transforming growth factor (TGF)-α 100/87, TGF-β1 60/33, insulin like growth factor-I 45/33, platelet-derived growth factor-A 55/67, basic fibroblast growth factor 0/0, hepatocyte growth factor (HGF) 50/53, EGF receptor 20/27, erb-B2 75/73, and HGF receptor (c-MET) 55/67. Semiquantitation of mRNA showed significantly lower expression of TGF-β1 (P<0.05) in UC. Differences in expression and mRNA levels were not statistically significant for any other GFs. Our results indicate that mucosa in chronic persistent UC has a low basal expression of TGF-β1 mRNA, and, since TGF-β1 is a multifunctional GF that plays important roles in regulating repair and regeneration following tissue injury, this low expression may be partially responsible for the intractability of the disease.

Key words

growth factors ulcerative colitis growth factor receptor RT-PCR mRNA 


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  1. 1.
    Podolsky DK. Inflammatory bowel discase. First of two parts. N Engl J Med 1991;325:928–937.PubMedGoogle Scholar
  2. 2.
    Sartor RB. Cytokines in intestinal inflammation: Pathophysiological and clinical consideration. Gastroenterology 1994;106:533–539.PubMedGoogle Scholar
  3. 3.
    Braegger CP, MacDonald TT. Immune mechanisms in chronic inflammatory bowel disease. Ann Allergy 1994;72:135–141.PubMedGoogle Scholar
  4. 4.
    Thompson JS, Saxena SK, Greaton C, et al. The effect of route of delivery of urogastrone on intestinal regeneration. Surgery 1989;106:45–51.PubMedGoogle Scholar
  5. 5.
    Olsen PS, Poulsen SS, Therkelsen K, et al. Oral administration of synthetic human urogastrone promotes healing of chronic duodenal ulcers in rats. Gastroenterology 1986;90:911–917.Google Scholar
  6. 6.
    Konturek SJ, Dembinski A, Warzecha T, et al. Role of epidermal growth factor in healing of chronic gastroduodenal ulcers in rats. Gastroenterology 1988;94:1300–1307.PubMedGoogle Scholar
  7. 7.
    Tarnawski A, Stachura J, Durbin T, et al. Increased expression of epidermal growth factor receptor during gastric ulcer healing in rats. Gastroenterology 1992;102:695–698.PubMedGoogle Scholar
  8. 8.
    Polk WH Jr, Dempsey PJ, Russell WE, et al. Increased production of transforming growth factor-α following acute gastric injury. Gastroenterology 1992;102:1467–1474.PubMedGoogle Scholar
  9. 9.
    Luck MS, Bass P. Effect of epidermal growth factor on experimental colitis in rats. J Pharmacol Exp Ther 1993;264:984–990.PubMedGoogle Scholar
  10. 10.
    McKenna KJ, Ligato S, Kauffman GL Jr, et al. Epidermal growth factor enhances intestinal mitotic activity and DNA content after acute abdominal radiation. Surgery 1994;115:626–632.PubMedGoogle Scholar
  11. 11.
    Kajikawa K, Yasui W, Sumiyoshi H, et al. Expression of epidermal growth factor in human tissues. Virchows Arch [A] 1994; 418:27–32.Google Scholar
  12. 12.
    Koretz K, Schlag P, Moller P. Expression of epidermal growth factor receptor in normal colorectal mucosa, adenoma and carcinoma. Virchows Arch [A] 1990;416:343–349.Google Scholar
  13. 13.
    Borlinghaus P, Wieser S, Lamerz R. Epidermal growth factor, transforming growth factor-α and epidermal growth factor receptor content in normal and carcinomatous gastric and colonic tissue. Clin Invest 1993;71:903–907.CrossRefGoogle Scholar
  14. 14.
    Bennett NT, Schultz GS. Growth factors and wound healing: Biochemical properties of growth factors and their receptors. Am J Surg 1993;165:728–737.PubMedGoogle Scholar
  15. 15.
    Hom DB, Maisel RH. Angiogenic growth factors: Their effects and potential in soft tissue wound healing. Ann Otol Rhinol Laryngol 1992;101:349–354.PubMedGoogle Scholar
  16. 16.
    Boros P, Miller CM. Hepatocyte growth factor: A multifunctional cytokine. Lancet 1995;345:293–295.CrossRefPubMedGoogle Scholar
  17. 17.
    Watanabe S, Hirose M, Wang XE, et al. Hepatocyte growth factor accelerates the wound repair of cultured gastric mucosal cells. Biochem Biophys Res Commun 1994;199:1453–1460.PubMedGoogle Scholar
  18. 18.
    Chromczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987;162:156–159.Google Scholar
  19. 19.
    Fukuda R, Satoh S, Nguyen XT, et al. Expression rate of cytokine mRNA in the liver of chronic hepatitis C: Comparison with chronic hepatitis B J Gastroenterol 1995;30:41–47.CrossRefPubMedGoogle Scholar
  20. 20.
    Yamamoto T, Ikawa S, Akiyama T, et al. Similarity of protein encoded by the human c-erb-B2 gene to epidermal growth factor receptor. Nature 1986;319:230–234.CrossRefPubMedGoogle Scholar
  21. 21.
    Prats H, Kaghad M, Prats AC, et al. High molecular mass forms of basic fibroblast growth factor are initiated by alternative CUG codons. Proc Natl Acad Sci USA 1989;86:1836–1840.PubMedGoogle Scholar
  22. 22.
    Nakamura T, Nishizawa T, Hagiya M, et al. Molecular cloning and expression of human hepatocyte growth factor. Nature 1989;342:440–443.CrossRefPubMedGoogle Scholar
  23. 23.
    Park M, Dean M, Kaul K, et al. Sequence of MET protooncogene cDNA has features characteristic of the tyrosine kinase family of growth-factor receptors. Proc Natl Acad Sci USA 1987;84:6379–6383.PubMedGoogle Scholar
  24. 24.
    Ralston SH, Hoey SA, Gallacher SJ, et al. Cylokine and growth factor expression in Pager's disease: Analysis by reverse-transcription polymerase reaction. Br J Rheumatol 1994;33:620–625.PubMedGoogle Scholar
  25. 25.
    Hull MA, Hawkey CJ. Low basic fibroblast growth factor levels in intact mucosa of gastric ulcer patients; evidence for a constitutional deficiency (abstract). Gut 1994;35[Suppl 5]:S50.Google Scholar
  26. 26.
    Mantyh CR, Vigna SR, Bollinger RR, et al. Differential expression of substance P receptors in patients with Crohn's disease and ulcerative colitis. Gastroenterology 1995;109:850–860.CrossRefPubMedGoogle Scholar
  27. 27.
    Yeh YL, Kang YM, Chaibi MS, et al. IL-1 and transforming growth factor-β inhibit platelet-derived growth factor-AA binding to osteoblastic cells by reducing platelet-derived growth factor-α receptor expression. J Immunol 1993;150:5625–5632.PubMedGoogle Scholar
  28. 28.
    Juan CD, Sanchez A, Nakamura T, et al. Hepatocyte growth factor up-regulates met expression in rat fetal hepatocytes in primary culture. Biochem Biophys Res Commun 1994;204:1364–1370.PubMedGoogle Scholar
  29. 29.
    Derynck R. Transforming growth factor alpha: Structure and biological activities. J Cell Biol 1986;31:293–304.Google Scholar
  30. 30.
    Ciardiello F, Kim N, Saeki T, et al. Differential expression of epidermal growth factor-related proteins in human colorectal tumors. Proc Natl Acad Sci USA 1991;88:7792–7796.PubMedGoogle Scholar
  31. 31.
    Wang D, Fujii S, Konishi I, et al. Expression of c-erbB-2 protein and epidermal growth factor receptor in normal tissues of the female genital tract and in the placenta. Virchows Arch [A] 1992;420:385–393.Google Scholar
  32. 32.
    Coussens L, Yang-Feng TL, Liao YC, et al. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science 1985;230:1132.PubMedGoogle Scholar
  33. 33.
    Tal M, Wetzler M, Josefberg Z. Sporadic amplification of the HER2/neu proto-oncogene in adenocarcinoma of various tissues. Cancer Res 1988;48:1517–1520.PubMedGoogle Scholar
  34. 34.
    Mueller RV, Spencer EM, Sommer A, et al. The role of IGF-I and IGFBP-3 in wound healing. In: Spencer EM (ed) Modern concepts of insulin-like growth factors. New York: Elsevier, 1991:185–192.Google Scholar
  35. 35.
    Lynch SE, Nixon JC, Colvin RB, Colvin RB, Antoniades HN. Role of platelet-derived growth factor in wound healing: Synergistic effects with other growth factors. Proc Natl Acad Sci USA 1987;84:7696–7700.PubMedGoogle Scholar
  36. 36.
    Cardo CC, Vlodavsky I, Friedman AH, et al. Expression of basic fibroblast growth factor in normal human tissues. Lab Invest 1990;63:832–840.Google Scholar
  37. 37.
    Nusrat A, Parkos CA, Bacarra AE, et al. Hepatocyte growth factor/scatter factor effects on epithelia: Regulation of intercellular junctions in transformed and nontransformed cell lines, basolateral polarization of c-MET receptor in transformed and natural intestinal epithelia, and induction of rapid wound repair in a transformed model epithelium. J Clin Invest 1994;93:2055–2065.Google Scholar
  38. 38.
    Tsujii M, Kawano S, Tsujii S, et al. Increased expression of c-MET messenger RNA following acute gastric injury in rats. Biochem Biopshys Res Commun 1994;200:536–541.Google Scholar
  39. 39.
    Border WA, Ruoslahti E. Transforming growth factor-β in discase: The dark side of tissue repair. J Clin Invest 1992;90:1–7.PubMedGoogle Scholar
  40. 40.
    Wahl SM. Transforming growth factor beta (TGF-β) in inflammation: A case and a cure. J Clin Immunol 1992;12:61–74.CrossRefPubMedGoogle Scholar
  41. 41.
    Reed JC, Abidi AH, Alpers JD, et al. Effect of cyclosporin A and dexamethasone on interleukin 2 receptor gene expression. J Immunol 1986;137:150–154.PubMedGoogle Scholar
  42. 42.
    Haynes AR, Shaw RJ. Dexamethasone-induced increase in platelet-derived growth factor β mRNA in human alveolar macrophages and myelomonocytic HL60 macrophage-like cells. Am J Respir Cell Mol Biol 1992;7:198–206.PubMedGoogle Scholar
  43. 43.
    Alexander RJ, Panja A, Liss EK, et al. Expression of growth factor receptor-encoded mRNA by colonic epithelial cells is altered in inflammatory bowel disease. Dig Dis Sci 1995;40:485–494.CrossRefPubMedGoogle Scholar
  44. 44.
    Sporn MG, Roberts AB. Peptide growth factors are multifunetional. Nature 1988;332:217–219.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • Aktaruzzaman Chowdhury
    • 1
  • Ryo Fukuda
    • 1
  • Shiro Fukumoto
    • 1
  1. 1.Second Department of Internal MedicineShimane Medical UniversityIzumo-shi, ShimaneJapan

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