Article Text

Download PDFPDF
Reversal of abnormal collagen production in Crohn’s disease intestinal biopsies treated with regenerating agents
  1. C Alexakis1,
  2. J P Caruelle1,
  3. A Sezeur2,
  4. J Cosnes3,
  5. J P Gendre3,
  6. H Mosnier2,
  7. L Beaugerie3,
  8. D Gallot4,
  9. M Malafosse4,
  10. D Barritault1,
  11. P Kern1
  1. 1CRRET/CNRS FRE 2412, Université Paris-12, 94010 Créteil Cedex, France
  2. 2Chirurgie Digestive et Colioscopique, Hôpital des Diaconesses, 75571 Paris Cedex 12, France
  3. 3Gastroentérologie, Hôpital Rothschild, 75571 Paris Cedex 12, France
  4. 4Chirurgie Générale, Hôpital Bichat, 75018 Paris, France
  1. Correspondence to:
    Professor D Barritault
    CRRET-CNRS FRE 2412, Faculté des Sciences de Créteil, Université Paris 12, Avenue du Général de Gaulle, 94010 Créteil cedex, France;


Background: Crohn’s disease (CD) is characterised by inflammation, muscle layer overgrowth, and collagenous fibrosis of the intestinal tract, with no effective therapy against collagen accumulation.

Aims: We quantified production of collagen in resection specimens from normal and CD patients and investigated the effect of regenerating agents (RGTAs) on collagen production. RGTAs are chemically substituted dextrans engineered to mimic the growth factor protecting effects of heparan sulphates. RGTAs have been shown to enhance tissue repair in various in vivo models and to modulate in vitro collagen phenotype differentially according to their structure.

Patients: We studied intestinal biopsies from two groups of CD patients: treated with glucocorticoids (CD-GC group: 10 patients) or not treated (CD group: seven patients), and from seven control patients.

Methods: After 24 hours of ex vivo incubation with (3H) proline, collagen I, III, and V were extracted by pepsin and quantitatively separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Biosynthesis of each collagen type was quantified on radiolabelled isolated collagen.

Results: Total intestinal collagen production in CD patients compared with controls was increased up to 3.5-fold overall (p<0.001). In particular, collagen III biosynthesis was enhanced by 6.2-fold (p<0.001) in CD patients. In the CD-GC group, collagen production abnormalities were less marked. RGTAs added to the incubation medium in the CD group decreased total collagen production by 50% and decreased collagen III synthesis by 76%.

Conclusion: This finding offers a rationale for using RGTAs in the treatment of intestinal fibrosis in CD, thus opening up a potential new therapeutic field for this family of drugs.

  • Crohn’s disease
  • fibrosis
  • collagen
  • regenerating agent
  • heparin mimetics
  • RGTA, regenerating agent
  • CD, Crohn’s disease
  • CD-GC, Crohn’s disease treated with glucocorticoids
  • TGF-β1, transforming growth factor β1
  • FGF-2, fibroblast growth factor 2
  • Mr, molecular weight
  • ds, degree of substitution
  • SDS-PAGE, sodium dodecyl sulphate-polyacrylamide gel electrophoresis

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.