Journal article
The Oxysterol Synthesising Enzyme CH25H Contributes to the Development of Intestinal Fibrosis.
- Raselli T Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich University, Zurich, Switzerland.
- Wyss A Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich University, Zurich, Switzerland.
- Gonzalez Alvarado MN Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich University, Zurich, Switzerland.
- Weder B Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich University, Zurich, Switzerland.
- Mamie C Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich University, Zurich, Switzerland.
- Spalinger MR Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich University, Zurich, Switzerland.
- Van Haaften WT Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich University, Zurich, Switzerland.
- Dijkstra G Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
- Sailer AW Chemical Biology & Therapeutics, Novartis Institutes for BioMedical Research, Basel, Switzerland.
- Imenez Silva PH Institute of Physiology, Zurich University, Zurich, Switzerland.
- Wagner CA Institute of Physiology, Zurich University, Zurich, Switzerland.
- Tosevski V Mass Cytometry Facility, Zurich University, Zurich, Switzerland.
- Leibl S Institute of Pathology and Molecular Pathology, University Hospital Zurich and Zurich University, Zurich, Switzerland.
- Scharl M Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich University, Zurich, Switzerland.
- Rogler G Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich University, Zurich, Switzerland.
- Hausmann M Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich University, Zurich, Switzerland.
- Misselwitz B Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich University, Zurich, Switzerland.
- 2019-06-21
Published in:
- Journal of Crohn's & colitis. - 2019
Fibrogenesis
cholesterol 25 hydroxylase [CH25H]
graft
intestinal fibrosis
mouse model
oxysterols
transplantation
Adult
Aged
Aged, 80 and over
Animals
Colitis
Crohn Disease
Dextran Sulfate
Disease Models, Animal
Female
Fibrosis
Humans
Intestines
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Middle Aged
Oxysterols
Steroid Hydroxylases
English
Intestinal fibrosis and stenosis are common complications of Crohn's disease [CD], frequently requiring surgery. Anti-inflammatory strategies can only partially prevent fibrosis; hence, anti-fibrotic therapies remain an unmet clinical need. Oxysterols are oxidised cholesterol derivatives with important roles in various biological processes. The enzyme cholesterol 25-hydroxylase [CH25H] converts cholesterol to 25-hydroxycholesterol [25-HC], which modulates immune responses and oxidative stress. In human intestinal samples from CD patients, we found a strong correlation of CH25H mRNA expression with the expression of fibrosis markers. We demonstrate reduced intestinal fibrosis in mice deficient for the CH25H enzyme, using the sodium dextran sulphate [DSS]-induced chronic colitis model. Additionally, using a heterotopic transplantation model of intestinal fibrosis, we demonstrate reduced collagen deposition and lower concentrations of hydroxyproline in CH25H knockouts. In the heterotopic transplant model, CH25H was expressed in fibroblasts. Taken together, our findings indicate an involvement of oxysterol synthesis in the pathogenesis of intestinal fibrosis.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1093/ecco-jcc/jjz039
- PMID 31220227
- Persistent URL
- https://sonar.ch/global/documents/199166
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