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Keratinocyte Growth Factor Ameliorates Dextran Sodium Sulfate Colitis in Mice

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Abstract

Keratinocyte growth factor (KGF) is emerging asan important mediator of mucosal defense and repair inthe colon. The aim of the present study was to evaluateand further characterize the effects of exogenous KGF administration utilizing the dextran sodiumsulfate (DSS) model of colitis in mice. Colitis wasinduced via oral administration of DSS (5 g/100 ml) toBalb/c mice for eight days. Intraperitonealadministration of KGF (5 mg/kg, once daily) or vehicle (VEH)was initiated 1 hr prior to the induction of the colitis(N = 10, each group). Mucosal injury of the entire colonwas histologically assessed and graded. An approximately fourfold reduction in the cryptdamage score was noted in the KGF group when compared tocontrols (VEH) (2.8 ± 1.03 and 11.4 ±0.78, respectively). The significant reduction ofmucosal injury in KGF treated mice confirms that KGF isa key mediator maintaining the integrity of the colonicmucosa.

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REFERENCES

  1. Bowen-Pope DF, Ross R: Platelet-derived growth factor. II. Specific binding to cultured cells. J Biol Chem 257:5161-5171, 1982

    Google Scholar 

  2. Roberts AB, Anzano MA, Wakefield LM, Roche NS, Stern DF, Sporn MB: Type beta transforming growth factor: A bifunctional regulator of cellular growth. Proc Natl Acad Sci USA 82:119-123, 1985

    Google Scholar 

  3. Itoh T, Suzuki M, Mitsui Y: Keratinocyte growth factor as a mitogen for primary culture of rat hepatocytes. Biochem Biophys Res Commun 192:1011-1015, 1993

    Google Scholar 

  4. Wahl SM, Hunt DA, Wakefield LM, McCartney-Francis N, Wahl LM, Roberts AB, Sporn MB: Transforming growth factor type beta induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sci USA 84:5788-5792, 1987

    Google Scholar 

  5. Raines EW, Dower SK, Ross R: Interleukin-1 mitogenic activity for fibroblasts and smooth muscle cells is due to PDGF-AA. Science 243:393-396, 1989

    Google Scholar 

  6. Gospodarowicz D, Neufeld G, Schweigerer L: Molecular and biological characterization of fibroblast growth factor, an angiogenic factor which also controls the proliferation and differentiation of mesoderm and neuroectoderm derived cells. Cell Differ 19:1-17, 1986

    Google Scholar 

  7. Schreiber AB, Winkler ME, Derynck R: Transforming growth factor-alpha: A more potent angiogenic mediator than epidermal growth factor. Science 232:1250-1253, 1986

    Google Scholar 

  8. Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM, Heine UI, Liotta LA, Falanga V, Kehrl JH: Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci USA 83:4167-4171, 1986

    Google Scholar 

  9. Chua CC, Geiman DE, Keller GH, Ladda RL: Induction of collagenase secretion in human fibroblast cultures by growth promoting factors. J Biol Chem 260:5213-5216, 1985

    Google Scholar 

  10. Greenhalgh DG, Sprugel KH, Murray MJ, Ross R: PDGF and FGF stimulate wound healing in the genetically diabetic mouse. Am J Pathol 136:1235-1246, 1990

    Google Scholar 

  11. Tsuboi R, Rifkin DB: Recombinant basic fibroblast growth factor stimulates wound healing in healing-impaired db/db mice. J Exp Med 172:245-251, 1990

    Google Scholar 

  12. Hebda PA, Klingbeil CK, Abraham JA, Fiddes JC: Basic fibroblast growth factor stimulation of epidermal wound healing in pigs. J Invest Dermatol 95:626-631, 1990

    Google Scholar 

  13. Aaronson SA, Bottaro DP, Miki T, Ron D, Finch PW, Fleming TP, Ahn JA, Taylor WG, Rubin JS: Keratinocyte growth factor. A fibroblast growth factor family member with unusual target cell specificity. Ann NY Acad Sci 638:62-77, 1991

    Google Scholar 

  14. Rubin JS, Osada H, Finch PW, Taylor WG, Rudikoff S, Aaronson SA: Purification and characterization of a newly identified growth factor specific for epithelial cells. Proc Natl Acad Sci USA 86:802-806, 1989

    Google Scholar 

  15. Finch PW, Rubin JS, Miki T, Ron D, Aaronson SA: Human KGF is FGF-related with properties of a paracrine effector of epithelial cell growth. Science 245:752-755, 1989

    Google Scholar 

  16. Werner S, Peters KG, Longaker MT, Fuller-Pace F, Banda MJ, Williams LT: Large induction of keratinocyte growth factor expression in the dermis during wound healing. Proc Natl Acad Sci USA 89:6896-6900, 1992

    Google Scholar 

  17. Staiano-Coico L, Krueger JG, Rubin JS, D'limi S, Vallat VP, Valentino L, Fahey T III, Hawes A, Kingston G, Madden MR, Mathwich M, Gottlieb AB, Aaronson SA: Human keratinocyte growth factor effects in a porcine model of epidermal wound healing. J Exp Med 178:865-878, 1993

    Google Scholar 

  18. Tsuboi R, Sato C, Kurita Y, Ron D, Rubin JS, Ogawa H: Keratinocyte growth factor (FGF-7) stimulates migration and plasminogen activator activity of normal human keratinocytes. J Invest Dermatol 101:49-53, 1993

    Google Scholar 

  19. Ulich TR, Yi ES, Longmuir K, Yin S, Blitz R, Morris CF, Housley RM, Pierce GF: Keratinocyte growth factor is a growth factor for type II pneumocyste s in vivo. J Clin Invest 93:1298-1306, 1994

    Google Scholar 

  20. Housley RM, Morris CF, Boyle W, Ring B, Blitz R, Tarpley JE, Devine PL, Whitehead RH, Pierce GF: Keratinocyte growth factor induces proliferation and differentiation of hepatocytes and epithelial cells throughout the rat gastrointestinal tract. J Clin Invest 94:1764-1777, 1994

    Google Scholar 

  21. Finch PW, Pricolo V, Wu A, Finkelstein SD: Increase d expression of keratinocyte growth factor messenger RNA associated with inflammatory bowel disease. Gastroenterology 110:441-451, 1996

    Google Scholar 

  22. Brauchle M, Madlener M, Wagner AD, Angermeyer K, Lauer U, Hofschneider PH, Gregor M, Werner S: Keratinocyte growth factor is highly overexpressed in inflammatory bowel disease. Am J Pathol 149:521-529, 1996

    Google Scholar 

  23. Finch PW, Cheng AL, Derald H: Determination of the cellular basis of keratinocyte growth factor overexpression in inflammatory bowel disease. Gastroenterology 112( suppl):A972, 1997

    Google Scholar 

  24. Zeeh JM, Proccacino F, Hoffmann P, Aukerman SL, McRoberts JA, Soltani S, Pierce GF, Lakshmanan J, Lacey D, Eysselein VE: Keratinocyte growth factor ameliorates mucosal injury in an experimental mode l of colit is in rats. Gastroenterology 110:1077-1083, 1996

    Google Scholar 

  25. Ni J, Chen SF, Hollander D: Effects of dextran sulphate sodium on intestinal epithelial cells and intestinal lymphocytes. Gut 39:234-241, 1996

    Google Scholar 

  26. Leung FW, Heng MCY, Allen S, Seno K, Lam K, Leung JWC, Heng MK: Time course of immunological events in dextran sulfate sodium-induced colitis in rats: an immunohistochemical and ultrastructural study. Gastroenterology 112( suppl):A1026, 1997

    Google Scholar 

  27. Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R: A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology 98:694-702, 1990

    Google Scholar 

  28. Cooper HS, Murthy SNS, Shah RS, Sedergran DJ: Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 69:238-249, 1993

    Google Scholar 

  29. Murthy SN, Cooper HS, Shim H, Shah RS, Ibrahim SA, Sedergran DJ: Treatment of dextran sulfate sodium-induced murine colitis by intracolonic cyclosporin. Dig Dis Sci 38:1722-1723, 1993

    Google Scholar 

  30. Iwanaga T, Hoshi O, Han H, Fujita T: Morphological analysis of acute ulcerative colitis experimentally induced by dextran sulfate sodium in the guinea pig: Some possible mechanisms of cecalulceration. J Gastroenterol 29:430-438, 1994

    Google Scholar 

  31. Satoyoshi K, Akita Y, Nozu F, Yoshikawa N, Mitamura K: Hemodynamics in the colonic mucosa of rats with dextran sulfate-induced colitis in the early phase. J Gastroenterol 31:512-517, 1996

    Google Scholar 

  32. Shintani N, Nakajima T, Nagai H, Watanabe M, Kagitani Y, Takizawa H, Asakura H: Immunological effect of immunoglobulin on experimental colitis induced by dextran sulfate. Nippon Shokakibyo Gakkai Zasshi 92:1911-1921, 1995 ( in Japanese)

    Google Scholar 

  33. Takizawa H, Shintani N, Natsui M, Sasakawa T, Nakakubo H, Nakajima T, Asakura H: Activated immunocompetent cells in rat colitis mucosa induced by dextran sulfate sodium and not complete but partial suppression of colitis by FK506. Digestion 56:259-264, 1995

    Google Scholar 

  34. Pentney PT, Bubenik GA: Melatonin reduces the severity of dextran-induced colitis in mice. J Pineal Res 19:31-39, 1995

    Google Scholar 

  35. Egger B, Proccacino F, Lakshmanan J, Reinshagen M, Hoffmann P, Patel A, Reuben W, Gnanakkan S, Liu L, Barajas L, Eysselein VE: Mice lacking transforming growth factor-alpha have an increased susceptibility to dextran sulfate induced colitis. Gastroenterology 113:825-832, 1997

    Google Scholar 

  36. Lev R, Spicer SS: Specific staining of sulfate groups with alcian blue at low pH. J Histochem Cytochem 12:309-311, 1964

    Google Scholar 

  37. Egger B, Patel A, Procaccino F, Eysselein VE: Dextran sodium sulfate (DSS) induced mucosal injury in mice depends on the concentration of the DSS solution but not on the dose of DSS administered. Gastroenterology 112(suppl):A964, 1997

    Google Scholar 

  38. Dignass AU, Tsunekawa S, Podolsky DK: Fibroblast growth factors modulate intestinal epithelial cell growth and migration. Gastroenterology 106:1254-1262, 1994

    Google Scholar 

  39. Pierce GF, Yanagihara D, Klopchin K, Danilenko DM, Hsu E, Kenney WC, Morris CF: Stimulation of all epithelial elements during skin regeneration by keratinocyte growth factor. J Exp Med 179:831-840, 1994

    Google Scholar 

  40. Dlugosz AA, Cheng C, Denning MF, Dempsey PJ, Coffey RJ Jr, Yuspa SH: Keratinocyte growth factor receptor ligands induce transforming growth factor alpha expression and activate the epidermal growth factor receptor signaling pathway in cultured epidermal keratinocytes. Cell Growth Differ 5:1283-1292, 1994

    Google Scholar 

  41. Yoshida S, Kasuga S, Hirao Y, Fuwa T, Nakagawa S: Effect of biosynthetic human epidermal growth factor on the synthesis and secretion of mucin glycoprotein from primary culture of rabbit fundal mucosa cells. In Vitro Cell Dev Biol 23:460-464, 1987

    Google Scholar 

  42. Grisham MB, Von Ritter C, Smith BF, LaMont JT, Granger DN: Interaction between oxygen radicals and gastric mucin. Am J Physiol 253:G93-G96, 1987

    Google Scholar 

  43. Mashimo H, Wu DC, Podolsky DK, Fishman MC: Impaired defense of intestinal mucosa in mice lacking intestinal trefoil factor. Science 274:259-265, 1996

    Google Scholar 

  44. Chinery R, Poulsom R, Rogers LA, Jeffery RE, Longcroft JM, Hanby AM, Wright NA: Localization of intestinal trefoil-factor mRNA in rat stomach and intestine by hybridization in situ. Biochem J 285:5-8, 1992

    Google Scholar 

  45. Kindon H, Pothoulakis C, Thim L, Lynch-Devaney K, Podolsky DK: Trefoil peptide protection of intestinal epithelial barrier function: cooperative interaction with mucinglycoprotein. Gastroenterology 109:516-523, 1995

    Google Scholar 

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Egger, B., Procaccino, F., Sarosi, I. et al. Keratinocyte Growth Factor Ameliorates Dextran Sodium Sulfate Colitis in Mice. Dig Dis Sci 44, 836–844 (1999). https://doi.org/10.1023/A:1026642715764

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