Publication

Intestinal Activation of pH-Sensing Receptor OGR1 [GPR68] Contributes to Fibrogenesis

Hutter, S., van Haaften, W. T., Huenerwadel, A., Baebler, K., Herfarth, N., Raselli, T., Mamie, C., Misselwitz, B., Rogler, G., Weder, B., Dijkstra, G., Meier, C. F., de Valliere, C., Weber, A., Imenez Silva, P. H., Wagner, C. A., Frey-Wagner, I., Ruiz, P. A. & Hausmann, M., 15-Nov-2018, In : Journal of Crohn's and Colitis. 12, 11, p. 1348-1358 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Hutter, S., van Haaften, W. T., Huenerwadel, A., Baebler, K., Herfarth, N., Raselli, T., ... Hausmann, M. (2018). Intestinal Activation of pH-Sensing Receptor OGR1 [GPR68] Contributes to Fibrogenesis. Journal of Crohn's and Colitis, 12(11), 1348-1358. https://doi.org/10.1093/ecco-jcc/jjy118

Author

Hutter, Senta ; van Haaften, Wouter T. ; Huenerwadel, Anouk ; Baebler, Katharina ; Herfarth, Neel ; Raselli, Tina ; Mamie, Celine ; Misselwitz, Benjamin ; Rogler, Gerhard ; Weder, Bruce ; Dijkstra, Gerard ; Meier, Chantal Florence ; de Valliere, Cheryl ; Weber, Achim ; Imenez Silva, Pedro H. ; Wagner, Carsten A. ; Frey-Wagner, Isabelle ; Ruiz, Pedro A. ; Hausmann, Martin. / Intestinal Activation of pH-Sensing Receptor OGR1 [GPR68] Contributes to Fibrogenesis. In: Journal of Crohn's and Colitis. 2018 ; Vol. 12, No. 11. pp. 1348-1358.

Harvard

Hutter, S, van Haaften, WT, Huenerwadel, A, Baebler, K, Herfarth, N, Raselli, T, Mamie, C, Misselwitz, B, Rogler, G, Weder, B, Dijkstra, G, Meier, CF, de Valliere, C, Weber, A, Imenez Silva, PH, Wagner, CA, Frey-Wagner, I, Ruiz, PA & Hausmann, M 2018, 'Intestinal Activation of pH-Sensing Receptor OGR1 [GPR68] Contributes to Fibrogenesis', Journal of Crohn's and Colitis, vol. 12, no. 11, pp. 1348-1358. https://doi.org/10.1093/ecco-jcc/jjy118

Standard

Intestinal Activation of pH-Sensing Receptor OGR1 [GPR68] Contributes to Fibrogenesis. / Hutter, Senta; van Haaften, Wouter T.; Huenerwadel, Anouk; Baebler, Katharina; Herfarth, Neel; Raselli, Tina; Mamie, Celine; Misselwitz, Benjamin; Rogler, Gerhard; Weder, Bruce; Dijkstra, Gerard; Meier, Chantal Florence; de Valliere, Cheryl; Weber, Achim; Imenez Silva, Pedro H.; Wagner, Carsten A.; Frey-Wagner, Isabelle; Ruiz, Pedro A.; Hausmann, Martin.

In: Journal of Crohn's and Colitis, Vol. 12, No. 11, 15.11.2018, p. 1348-1358.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Hutter S, van Haaften WT, Huenerwadel A, Baebler K, Herfarth N, Raselli T et al. Intestinal Activation of pH-Sensing Receptor OGR1 [GPR68] Contributes to Fibrogenesis. Journal of Crohn's and Colitis. 2018 Nov 15;12(11):1348-1358. https://doi.org/10.1093/ecco-jcc/jjy118


BibTeX

@article{56626491a6214adb905d1d153414b1c0,
title = "Intestinal Activation of pH-Sensing Receptor OGR1 [GPR68] Contributes to Fibrogenesis",
abstract = "Background and Aims: pH-sensing ovarian cancer G-protein coupled receptor-1 [OGR1/GPR68] is regulated by key inflammatory cytokines. Patients suffering from inflammatory bowel diseases [IBDs] express increased mucosal levels of OGR1 compared with non-IBD controls. pH-sensing may be relevant for progression of fibrosis, as extracellular acidification leads to fibroblast activation and extracellular matrix remodelling. We aimed to determine OGR1 expression in fibrotic lesions in the intestine of Crohn's disease [CD] patients, and the effect of Ogr1 deficiency in fibrogenesis.Methods: Human fibrotic and non-fibrotic terminal ileum was obtained from CD patients undergoing ileocaecal resection due to stenosis. Gene expression of fibrosis markers and pH-sensing receptors was analysed. For the initiation of fibrosis in vivo, spontaneous colitis by Il10(-/-), dextran sodium sulfate [DSS]-induced chronic colitis and the heterotopic intestinal transplantation model were used.Results: Increased expression of fibrosis markers was accompanied by an increase in OGR1 [2.71 +/- 0.69 vs 1.18 +/- 0.03, p = 0.016] in fibrosis-affected human terminal ileum, compared with the non-fibrotic resection margin. Positive correlation between OGR1 expression and pro-fibrotic cytokines [TGFB1 and CTGF] and pro-collagens was observed. The heterotopic animal model for intestinal fibrosis transplanted with terminal ileum from Ogr1-/-mice showed a decrease in mRNA expression of fibrosis markers as well as a decrease in collagen layer thickness and hydroxyproline compared with grafts from wild-type mice.Conclusions: OGR1 expression was correlated with increased expression levels of pro-fibrotic genes and collagen deposition. Ogr1 deficiency was associated with a decrease in fibrosis formation. Targeting OGR1 may be a potential new treatment option for IBD-associated fibrosis.",
keywords = "Fibrosis, Crohn's disease, IBD models, PROTEIN-COUPLED RECEPTORS, INFLAMMATORY-BOWEL-DISEASE, AIRWAY SMOOTH-MUSCLE, CROHNS-DISEASE, EPITHELIAL-CELLS, NATURAL-HISTORY, GROWTH-FACTOR, FIBROSIS, COLITIS, TGF-BETA-1",
author = "Senta Hutter and {van Haaften}, {Wouter T.} and Anouk Huenerwadel and Katharina Baebler and Neel Herfarth and Tina Raselli and Celine Mamie and Benjamin Misselwitz and Gerhard Rogler and Bruce Weder and Gerard Dijkstra and Meier, {Chantal Florence} and {de Valliere}, Cheryl and Achim Weber and {Imenez Silva}, {Pedro H.} and Wagner, {Carsten A.} and Isabelle Frey-Wagner and Ruiz, {Pedro A.} and Martin Hausmann",
year = "2018",
month = "11",
day = "15",
doi = "10.1093/ecco-jcc/jjy118",
language = "English",
volume = "12",
pages = "1348--1358",
journal = "Journal of Crohn's and Colitis",
issn = "1873-9946",
publisher = "Oxford University Press",
number = "11",

}

RIS

TY - JOUR

T1 - Intestinal Activation of pH-Sensing Receptor OGR1 [GPR68] Contributes to Fibrogenesis

AU - Hutter, Senta

AU - van Haaften, Wouter T.

AU - Huenerwadel, Anouk

AU - Baebler, Katharina

AU - Herfarth, Neel

AU - Raselli, Tina

AU - Mamie, Celine

AU - Misselwitz, Benjamin

AU - Rogler, Gerhard

AU - Weder, Bruce

AU - Dijkstra, Gerard

AU - Meier, Chantal Florence

AU - de Valliere, Cheryl

AU - Weber, Achim

AU - Imenez Silva, Pedro H.

AU - Wagner, Carsten A.

AU - Frey-Wagner, Isabelle

AU - Ruiz, Pedro A.

AU - Hausmann, Martin

PY - 2018/11/15

Y1 - 2018/11/15

N2 - Background and Aims: pH-sensing ovarian cancer G-protein coupled receptor-1 [OGR1/GPR68] is regulated by key inflammatory cytokines. Patients suffering from inflammatory bowel diseases [IBDs] express increased mucosal levels of OGR1 compared with non-IBD controls. pH-sensing may be relevant for progression of fibrosis, as extracellular acidification leads to fibroblast activation and extracellular matrix remodelling. We aimed to determine OGR1 expression in fibrotic lesions in the intestine of Crohn's disease [CD] patients, and the effect of Ogr1 deficiency in fibrogenesis.Methods: Human fibrotic and non-fibrotic terminal ileum was obtained from CD patients undergoing ileocaecal resection due to stenosis. Gene expression of fibrosis markers and pH-sensing receptors was analysed. For the initiation of fibrosis in vivo, spontaneous colitis by Il10(-/-), dextran sodium sulfate [DSS]-induced chronic colitis and the heterotopic intestinal transplantation model were used.Results: Increased expression of fibrosis markers was accompanied by an increase in OGR1 [2.71 +/- 0.69 vs 1.18 +/- 0.03, p = 0.016] in fibrosis-affected human terminal ileum, compared with the non-fibrotic resection margin. Positive correlation between OGR1 expression and pro-fibrotic cytokines [TGFB1 and CTGF] and pro-collagens was observed. The heterotopic animal model for intestinal fibrosis transplanted with terminal ileum from Ogr1-/-mice showed a decrease in mRNA expression of fibrosis markers as well as a decrease in collagen layer thickness and hydroxyproline compared with grafts from wild-type mice.Conclusions: OGR1 expression was correlated with increased expression levels of pro-fibrotic genes and collagen deposition. Ogr1 deficiency was associated with a decrease in fibrosis formation. Targeting OGR1 may be a potential new treatment option for IBD-associated fibrosis.

AB - Background and Aims: pH-sensing ovarian cancer G-protein coupled receptor-1 [OGR1/GPR68] is regulated by key inflammatory cytokines. Patients suffering from inflammatory bowel diseases [IBDs] express increased mucosal levels of OGR1 compared with non-IBD controls. pH-sensing may be relevant for progression of fibrosis, as extracellular acidification leads to fibroblast activation and extracellular matrix remodelling. We aimed to determine OGR1 expression in fibrotic lesions in the intestine of Crohn's disease [CD] patients, and the effect of Ogr1 deficiency in fibrogenesis.Methods: Human fibrotic and non-fibrotic terminal ileum was obtained from CD patients undergoing ileocaecal resection due to stenosis. Gene expression of fibrosis markers and pH-sensing receptors was analysed. For the initiation of fibrosis in vivo, spontaneous colitis by Il10(-/-), dextran sodium sulfate [DSS]-induced chronic colitis and the heterotopic intestinal transplantation model were used.Results: Increased expression of fibrosis markers was accompanied by an increase in OGR1 [2.71 +/- 0.69 vs 1.18 +/- 0.03, p = 0.016] in fibrosis-affected human terminal ileum, compared with the non-fibrotic resection margin. Positive correlation between OGR1 expression and pro-fibrotic cytokines [TGFB1 and CTGF] and pro-collagens was observed. The heterotopic animal model for intestinal fibrosis transplanted with terminal ileum from Ogr1-/-mice showed a decrease in mRNA expression of fibrosis markers as well as a decrease in collagen layer thickness and hydroxyproline compared with grafts from wild-type mice.Conclusions: OGR1 expression was correlated with increased expression levels of pro-fibrotic genes and collagen deposition. Ogr1 deficiency was associated with a decrease in fibrosis formation. Targeting OGR1 may be a potential new treatment option for IBD-associated fibrosis.

KW - Fibrosis

KW - Crohn's disease

KW - IBD models

KW - PROTEIN-COUPLED RECEPTORS

KW - INFLAMMATORY-BOWEL-DISEASE

KW - AIRWAY SMOOTH-MUSCLE

KW - CROHNS-DISEASE

KW - EPITHELIAL-CELLS

KW - NATURAL-HISTORY

KW - GROWTH-FACTOR

KW - FIBROSIS

KW - COLITIS

KW - TGF-BETA-1

U2 - 10.1093/ecco-jcc/jjy118

DO - 10.1093/ecco-jcc/jjy118

M3 - Article

C2 - 30165600

VL - 12

SP - 1348

EP - 1358

JO - Journal of Crohn's and Colitis

JF - Journal of Crohn's and Colitis

SN - 1873-9946

IS - 11

ER -

ID: 76433818