Biomarkers, Models and Mechanisms of Intestinal Fibrosis

van Haaften, T., 2019, [Groningen]: Rijksuniversiteit Groningen. 207 p.

Research output: ThesisThesis fully internal (DIV)Academic

Copy link to clipboard


  • Title and contents

    Final publisher's version, 82 KB, PDF-document

  • Chapter 1

    Final publisher's version, 7 MB, PDF-document

  • Chapter 2

    Final publisher's version, 1 MB, PDF-document

  • Chapter 3

    Final publisher's version, 1 MB, PDF-document

    Embargo ends: 11/09/2020

    Request copy

  • Chapter 4

    Final publisher's version, 9 MB, PDF-document

    Embargo ends: 11/09/2020

    Request copy

  • Chapter 5

    Final publisher's version, 2 MB, PDF-document

    Embargo ends: 11/09/2020

    Request copy

  • Chapter 6

    Final publisher's version, 4 MB, PDF-document

  • Chapter 7

    Final publisher's version, 4 MB, PDF-document

  • Chapter 8

    Final publisher's version, 960 KB, PDF-document

  • Chapter 9

    Final publisher's version, 727 KB, PDF-document

  • Chapter 10

    Final publisher's version, 900 KB, PDF-document

  • Complete thesis

    Final publisher's version, 26 MB, PDF-document

    Embargo ends: 11/09/2020

    Request copy

  • Propositions

    Final publisher's version, 22 KB, PDF-document


Chronic intestinal inflammation in Crohn’s disease (CD) frequently causes complications such as fibrosis or fistulae. Intestinal fibrosis is characterized by excessive deposition of collagens and causing stenosis and finally intestinal obstruction. Fistulae on the other hand are characterized by a relative decrease in deposition of collagens due to persistent inflammation. Despite advances in treatment with anti-inflammatory drugs, the incidence of fibrosis and fistulae remains high. Repetitive endoscopic dilatation of stenosis, or surgery for fibrosis or fistulae are so far the only therapeutic options. Furthermore, currently no serological biomarkers are available to detect the presence of intestinal fibrosis or fistulae.

The development of drugs against intestinal fibrosis/fistulae is being hampered by the lack of insight in the underlying mechanism and by the lack of translational models that can predict drug efficacy in humans. We describe a novel translational ex vivo model for intestinal fibrosis, which could bridge the gap between pre-clinical and clinical research to evaluate the efficacy of anti-fibrotic drugs in man. In addition, pH sensing receptor ovarian cancer G-protein coupled receptor-1 was confirmed to be part of the mechanism of inducing intestinal fibrosis and may be a target for CD-associated fibrosis. Furthermore, we propose targets to inhibit intestinal fibrosis and existing drugs acting on these targets, based on increased mRNA expression of enzymes involved in the post-translational collagen processing of intestinal fibrosis affected tissue. Finally, we provide evidence for the use of serological markers related to turnover of extra cellular matrix to detect the presence of penetrating CD.
Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
Award date11-Sep-2019
Place of Publication[Groningen]
Print ISBNs978-94-034-1885-8
Electronic ISBNs978-94-034-1884-1
Publication statusPublished - 2019

View graph of relations

Download statistics

No data available

ID: 96088661