The Oxysterol Synthesising Enzyme CH25H Contributes to the Development of Intestinal FibrosisRaselli, T., Wyss, A., Alvarado, M. N. G., Weder, B., Mamie, C., Spalinger, M. R., van Haaften, W. T., Dijkstra, G., Sailer, A. W., Silva, P. H. I., Wagner, C. A., Tosevski, V., Leibl, S., Scharl, M., Rogler, G., Hausmann, M. & Misselwitz, B., Sep-2019, In : Journal of Crohn's and Colitis. 13, 9, p. 1186-1200 15 p.
Research output: Contribution to journal › Article › Academic › peer-review
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.
|Number of pages||15|
|Journal||Journal of Crohn's and Colitis|
|Publication status||Published - Sep-2019|
- Fibrogenesis, intestinal fibrosis, cholesterol 25 hydroxylase [CH25H], oxysterols, transplantation, graft, mouse model, ACID PHENETHYL ESTER, NF-KAPPA-B, CAFFEIC ACID, CHOLESTEROL 25-HYDROXYLASE, CROHNS-DISEASE, ULCERATIVE-COLITIS, PULMONARY-FIBROSIS, LIVER FIBROSIS, CELL-MIGRATION, TGF-BETA