Publication

The Oxysterol Synthesising Enzyme CH25H Contributes to the Development of Intestinal Fibrosis

Raselli, 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 journalArticleAcademicpeer-review

APA

Raselli, T., Wyss, A., Alvarado, M. N. G., Weder, B., Mamie, C., Spalinger, M. R., ... Misselwitz, B. (2019). The Oxysterol Synthesising Enzyme CH25H Contributes to the Development of Intestinal Fibrosis. Journal of Crohn's and Colitis, 13(9), 1186-1200. https://doi.org/10.1093/ecco-jcc/jjz039

Author

Raselli, T. ; Wyss, A. ; Alvarado, M. N. Gonzalez ; Weder, B. ; Mamie, C. ; Spalinger, M. R. ; van Haaften, W. T. ; Dijkstra, G. ; Sailer, A. W. ; Silva, P. H. Imenez ; Wagner, C. A. ; Tosevski, V. ; Leibl, Sebastian ; Scharl, M. ; Rogler, G. ; Hausmann, M. ; Misselwitz, B. / The Oxysterol Synthesising Enzyme CH25H Contributes to the Development of Intestinal Fibrosis. In: Journal of Crohn's and Colitis. 2019 ; Vol. 13, No. 9. pp. 1186-1200.

Harvard

Raselli, T, Wyss, A, Alvarado, MNG, Weder, B, Mamie, C, Spalinger, MR, van Haaften, WT, Dijkstra, G, Sailer, AW, Silva, PHI, Wagner, CA, Tosevski, V, Leibl, S, Scharl, M, Rogler, G, Hausmann, M & Misselwitz, B 2019, 'The Oxysterol Synthesising Enzyme CH25H Contributes to the Development of Intestinal Fibrosis', Journal of Crohn's and Colitis, vol. 13, no. 9, pp. 1186-1200. https://doi.org/10.1093/ecco-jcc/jjz039

Standard

The Oxysterol Synthesising Enzyme CH25H Contributes to the Development of Intestinal Fibrosis. / Raselli, T.; Wyss, A.; Alvarado, M. N. Gonzalez; Weder, B.; Mamie, C.; Spalinger, M. R.; van Haaften, W. T.; Dijkstra, G.; Sailer, A. W.; Silva, P. H. Imenez; Wagner, C. A.; Tosevski, V.; Leibl, Sebastian; Scharl, M.; Rogler, G.; Hausmann, M.; Misselwitz, B.

In: Journal of Crohn's and Colitis, Vol. 13, No. 9, 09.2019, p. 1186-1200.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Raselli T, Wyss A, Alvarado MNG, Weder B, Mamie C, Spalinger MR et al. The Oxysterol Synthesising Enzyme CH25H Contributes to the Development of Intestinal Fibrosis. Journal of Crohn's and Colitis. 2019 Sep;13(9):1186-1200. https://doi.org/10.1093/ecco-jcc/jjz039


BibTeX

@article{c1ef6b2a6d064c6e9a3839e820108119,
title = "The Oxysterol Synthesising Enzyme CH25H Contributes to the Development of Intestinal Fibrosis",
abstract = "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.",
keywords = "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",
author = "T. Raselli and A. Wyss and Alvarado, {M. N. Gonzalez} and B. Weder and C. Mamie and Spalinger, {M. R.} and {van Haaften}, {W. T.} and G. Dijkstra and Sailer, {A. W.} and Silva, {P. H. Imenez} and Wagner, {C. A.} and V. Tosevski and Sebastian Leibl and M. Scharl and G. Rogler and M. Hausmann and B. Misselwitz",
year = "2019",
month = "9",
doi = "10.1093/ecco-jcc/jjz039",
language = "English",
volume = "13",
pages = "1186--1200",
journal = "Journal of Crohn's and Colitis",
issn = "1873-9946",
publisher = "Oxford University Press",
number = "9",

}

RIS

TY - JOUR

T1 - The Oxysterol Synthesising Enzyme CH25H Contributes to the Development of Intestinal Fibrosis

AU - Raselli, T.

AU - Wyss, A.

AU - Alvarado, M. N. Gonzalez

AU - Weder, B.

AU - Mamie, C.

AU - Spalinger, M. R.

AU - van Haaften, W. T.

AU - Dijkstra, G.

AU - Sailer, A. W.

AU - Silva, P. H. Imenez

AU - Wagner, C. A.

AU - Tosevski, V.

AU - Leibl, Sebastian

AU - Scharl, M.

AU - Rogler, G.

AU - Hausmann, M.

AU - Misselwitz, B.

PY - 2019/9

Y1 - 2019/9

N2 - 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.

AB - 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.

KW - Fibrogenesis

KW - intestinal fibrosis

KW - cholesterol 25 hydroxylase [CH25H]

KW - oxysterols

KW - transplantation

KW - graft

KW - mouse model

KW - ACID PHENETHYL ESTER

KW - NF-KAPPA-B

KW - CAFFEIC ACID

KW - CHOLESTEROL 25-HYDROXYLASE

KW - CROHNS-DISEASE

KW - ULCERATIVE-COLITIS

KW - PULMONARY-FIBROSIS

KW - LIVER FIBROSIS

KW - CELL-MIGRATION

KW - TGF-BETA

U2 - 10.1093/ecco-jcc/jjz039

DO - 10.1093/ecco-jcc/jjz039

M3 - Article

VL - 13

SP - 1186

EP - 1200

JO - Journal of Crohn's and Colitis

JF - Journal of Crohn's and Colitis

SN - 1873-9946

IS - 9

ER -

ID: 118195147