J.R. de Bruyn
- Fibrosis and vitamin D in inflammatory bowel diseases
- IBD considered from both basic and clinical perspectives
G.R. van den Brink
- Award date
- 29 June 2018
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
In the first part of this thesis we focused on fibrosis in inflammatory bowel disease. Fibrosis is the formation of excess extracellular matrix. Accumulation of extracellular matrix leads to increased tissue stiffness, as is the case in stenotic Crohn’s disease. We showed that human fibroblasts isolated from stenotic ileum displayed an aberrant response to stiff tissue environment with reduced activity of extracellular matrix degrading enzymes (matrix metalloproteinases). Inhibition of lysyl oxidase (LOX), an enzyme responsible for collagen crosslinking and hence tissue stiffness, restored the phenotype of stenotic fibroblasts to that of normal fibroblasts. These data identify LOX-inhibition as a potential anti-fibrotic agent in stenotic Crohn’s disease.
Until now very little is known about fibrosis in ulcerative colitis. We have shown that patients with ulcerative colitis have fibrosis, compared to control patients, and that fibrosis occurs already early during disease course.
In the second part we focused on vitamin D. Vitamin D has anti-inflammatory effects in vitro as well as in animal models for Crohn’s disease. First we have shown that Crohn’s disease patients have insufficient levels of vitamin D. We then report on a multicenter, double-blind, placebo-controlled trial with high dose vitamin D versus placebo in postoperative Crohn’s disease patients. We showed that high dose vitamin D treatment did not reduce the incidence of postoperative endoscopic and clinical recurrence in Crohn’s disease patients, despite doubling of serum vitamin D levels. It provides clues to vitamin D deficiency as a consequence of Crohn’s disease rather than a causal explanation in the pathophysiology of Crohn’s disease.
Thesis (complete) (Embargo up to and including 29 June 2020)
Chapter 6: High dose vitamin D does not prevent postoperative endoscopic and clinical recurrence in Crohn’s disease (Embargo up to and including 29 June 2020)
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