Publication

Evaluating the efficacy of potential drugs for intestinal fibrosis using precision-cut tissue slices

Iswandana, R., Pham, B. T., van Haaften, W., Oosterhuis, D., Mutsaers, H. & Olinga, P., 1-Feb-2015, In : Journal of Crohn's and Colitis. 9, suppl 1, p. s116 1 p.

Research output: Contribution to journalMeeting AbstractAcademic

APA

Iswandana, R., Pham, B. T., van Haaften, W., Oosterhuis, D., Mutsaers, H., & Olinga, P. (2015). Evaluating the efficacy of potential drugs for intestinal fibrosis using precision-cut tissue slices. Journal of Crohn's and Colitis, 9(suppl 1), s116. https://doi.org/10.1093/ecco-jcc/jju027.196

Author

Iswandana, Raditya ; Pham, B.T. ; van Haaften, Wouter ; Oosterhuis, Dorenda ; Mutsaers, Henricus ; Olinga, Peter. / Evaluating the efficacy of potential drugs for intestinal fibrosis using precision-cut tissue slices. In: Journal of Crohn's and Colitis. 2015 ; Vol. 9, No. suppl 1. pp. s116.

Harvard

Iswandana, R, Pham, BT, van Haaften, W, Oosterhuis, D, Mutsaers, H & Olinga, P 2015, 'Evaluating the efficacy of potential drugs for intestinal fibrosis using precision-cut tissue slices', Journal of Crohn's and Colitis, vol. 9, no. suppl 1, pp. s116. https://doi.org/10.1093/ecco-jcc/jju027.196

Standard

Evaluating the efficacy of potential drugs for intestinal fibrosis using precision-cut tissue slices. / Iswandana, Raditya; Pham, B.T.; van Haaften, Wouter; Oosterhuis, Dorenda; Mutsaers, Henricus; Olinga, Peter.

In: Journal of Crohn's and Colitis, Vol. 9, No. suppl 1, 01.02.2015, p. s116.

Research output: Contribution to journalMeeting AbstractAcademic

Vancouver

Iswandana R, Pham BT, van Haaften W, Oosterhuis D, Mutsaers H, Olinga P. Evaluating the efficacy of potential drugs for intestinal fibrosis using precision-cut tissue slices. Journal of Crohn's and Colitis. 2015 Feb 1;9(suppl 1):s116. https://doi.org/10.1093/ecco-jcc/jju027.196


BibTeX

@article{3298fed404c947a19af801201891eb51,
title = "Evaluating the efficacy of potential drugs for intestinal fibrosis using precision-cut tissue slices",
abstract = "Intestinal fibrosis (IF) is a common complication in Crohn's disease. Currently, there are no drugs registered to treat IF and the sole therapy is intestinal resection. Transforming growth factor (TGF)-beta and platelet-derived growth factor (PDGF) play a key role in IF and are the main targets for potential treatment. Recently, we developed a novel model for the early onset of IF using precision-cut intestinal slices (PCIS). Our objective was to investigate the antifibrotic effect of some potential antifibrotic compounds, including TGF-beta and PDGF-pathway inhibitors, by using the murine PCIS fibrosis model. Murine PCIS were incubated up to 48 h. The viability was assessed by evaluating the ATP content of the PCIS. Gene expression of the fibrosis markers pro-collagen 1a1 (Col1a1), heat shock protein 47 (Hsp47) and fibronectin (Fn2) were determined by qPCR. The effects of antifibrotic drugs mainly inhibiting the TGF-beta pathway: valproic acid (VPA), tetrandrine (Tet), pirfenidone (Pir), and LY2109761 (LY) and mainly inhibiting the PDGF pathway: imatinib (Ima), sorafenib (Sor), and sunitinib (Sun) were determined at the maximal non-toxic concentrations. Murine PCIS remained viable up to 48 h of incubation and showed increased gene expression of the fibrosis markers (Col1a1, 0.6; Hsp47, 4.0 and Fn2, 4.4 fold). After 48 h, VPA and Tet down-regulated Hsp47 gene expression 2.0 and 1.7 fold, respectively. Furthermore, Fn2 gene expression was also decreased 2.1 fold by Tet. Meanwhile, Pir decreased Col1a1, Hsp47, and Fn2 gene expression 2.2, 1.5, and 1.2 fold, respectively. All investigated markers of fibrosis were down-regulated by LY (Col1a1, 9.0; Hsp47, 1.9 and Fn2, 2.7 fold). Sun decreased the expression of Col1a1, 1.6; Hsp47, 3.3 and Fn2, 2.3 fold, while Sor only down-regulated Hsp47, 1.3 fold. In contrast, Ima did not affect the expression of fibrosis markers. From the compounds studied, the TGF-beta-inhibitors; Tet, Pir, and LY and only one PDGF-inhibitor, Sun, showed potential antifibrotic effect on gene expression of fibrosis markers in murine PCIS. Thus, PCIS is a promising model to evaluate the antifibrotic effect of potential drugs for intestinal fibrosis.",
keywords = "transforming growth factor beta1, platelet derived growth factor, heat shock protein 47, collagen type 1, alpha smooth muscle actin, fibronectin, connective tissue growth factor, intestinal fibrosis, mouse, jejunum, gene expression, valproic acid, tetrandrine, pirfenidone, ly2109761, imatinib, sorafenib, sunitinib",
author = "Raditya Iswandana and B.T. Pham and {van Haaften}, Wouter and Dorenda Oosterhuis and Henricus Mutsaers and Peter Olinga",
year = "2015",
month = "2",
day = "1",
doi = "10.1093/ecco-jcc/jju027.196",
language = "English",
volume = "9",
pages = "s116",
journal = "Journal of Crohn's and Colitis",
issn = "1873-9946",
publisher = "Oxford University Press",
number = "suppl 1",

}

RIS

TY - JOUR

T1 - Evaluating the efficacy of potential drugs for intestinal fibrosis using precision-cut tissue slices

AU - Iswandana, Raditya

AU - Pham, B.T.

AU - van Haaften, Wouter

AU - Oosterhuis, Dorenda

AU - Mutsaers, Henricus

AU - Olinga, Peter

PY - 2015/2/1

Y1 - 2015/2/1

N2 - Intestinal fibrosis (IF) is a common complication in Crohn's disease. Currently, there are no drugs registered to treat IF and the sole therapy is intestinal resection. Transforming growth factor (TGF)-beta and platelet-derived growth factor (PDGF) play a key role in IF and are the main targets for potential treatment. Recently, we developed a novel model for the early onset of IF using precision-cut intestinal slices (PCIS). Our objective was to investigate the antifibrotic effect of some potential antifibrotic compounds, including TGF-beta and PDGF-pathway inhibitors, by using the murine PCIS fibrosis model. Murine PCIS were incubated up to 48 h. The viability was assessed by evaluating the ATP content of the PCIS. Gene expression of the fibrosis markers pro-collagen 1a1 (Col1a1), heat shock protein 47 (Hsp47) and fibronectin (Fn2) were determined by qPCR. The effects of antifibrotic drugs mainly inhibiting the TGF-beta pathway: valproic acid (VPA), tetrandrine (Tet), pirfenidone (Pir), and LY2109761 (LY) and mainly inhibiting the PDGF pathway: imatinib (Ima), sorafenib (Sor), and sunitinib (Sun) were determined at the maximal non-toxic concentrations. Murine PCIS remained viable up to 48 h of incubation and showed increased gene expression of the fibrosis markers (Col1a1, 0.6; Hsp47, 4.0 and Fn2, 4.4 fold). After 48 h, VPA and Tet down-regulated Hsp47 gene expression 2.0 and 1.7 fold, respectively. Furthermore, Fn2 gene expression was also decreased 2.1 fold by Tet. Meanwhile, Pir decreased Col1a1, Hsp47, and Fn2 gene expression 2.2, 1.5, and 1.2 fold, respectively. All investigated markers of fibrosis were down-regulated by LY (Col1a1, 9.0; Hsp47, 1.9 and Fn2, 2.7 fold). Sun decreased the expression of Col1a1, 1.6; Hsp47, 3.3 and Fn2, 2.3 fold, while Sor only down-regulated Hsp47, 1.3 fold. In contrast, Ima did not affect the expression of fibrosis markers. From the compounds studied, the TGF-beta-inhibitors; Tet, Pir, and LY and only one PDGF-inhibitor, Sun, showed potential antifibrotic effect on gene expression of fibrosis markers in murine PCIS. Thus, PCIS is a promising model to evaluate the antifibrotic effect of potential drugs for intestinal fibrosis.

AB - Intestinal fibrosis (IF) is a common complication in Crohn's disease. Currently, there are no drugs registered to treat IF and the sole therapy is intestinal resection. Transforming growth factor (TGF)-beta and platelet-derived growth factor (PDGF) play a key role in IF and are the main targets for potential treatment. Recently, we developed a novel model for the early onset of IF using precision-cut intestinal slices (PCIS). Our objective was to investigate the antifibrotic effect of some potential antifibrotic compounds, including TGF-beta and PDGF-pathway inhibitors, by using the murine PCIS fibrosis model. Murine PCIS were incubated up to 48 h. The viability was assessed by evaluating the ATP content of the PCIS. Gene expression of the fibrosis markers pro-collagen 1a1 (Col1a1), heat shock protein 47 (Hsp47) and fibronectin (Fn2) were determined by qPCR. The effects of antifibrotic drugs mainly inhibiting the TGF-beta pathway: valproic acid (VPA), tetrandrine (Tet), pirfenidone (Pir), and LY2109761 (LY) and mainly inhibiting the PDGF pathway: imatinib (Ima), sorafenib (Sor), and sunitinib (Sun) were determined at the maximal non-toxic concentrations. Murine PCIS remained viable up to 48 h of incubation and showed increased gene expression of the fibrosis markers (Col1a1, 0.6; Hsp47, 4.0 and Fn2, 4.4 fold). After 48 h, VPA and Tet down-regulated Hsp47 gene expression 2.0 and 1.7 fold, respectively. Furthermore, Fn2 gene expression was also decreased 2.1 fold by Tet. Meanwhile, Pir decreased Col1a1, Hsp47, and Fn2 gene expression 2.2, 1.5, and 1.2 fold, respectively. All investigated markers of fibrosis were down-regulated by LY (Col1a1, 9.0; Hsp47, 1.9 and Fn2, 2.7 fold). Sun decreased the expression of Col1a1, 1.6; Hsp47, 3.3 and Fn2, 2.3 fold, while Sor only down-regulated Hsp47, 1.3 fold. In contrast, Ima did not affect the expression of fibrosis markers. From the compounds studied, the TGF-beta-inhibitors; Tet, Pir, and LY and only one PDGF-inhibitor, Sun, showed potential antifibrotic effect on gene expression of fibrosis markers in murine PCIS. Thus, PCIS is a promising model to evaluate the antifibrotic effect of potential drugs for intestinal fibrosis.

KW - transforming growth factor beta1

KW - platelet derived growth factor

KW - heat shock protein 47

KW - collagen type 1

KW - alpha smooth muscle actin

KW - fibronectin

KW - connective tissue growth factor

KW - intestinal fibrosis

KW - mouse

KW - jejunum

KW - gene expression

KW - valproic acid

KW - tetrandrine

KW - pirfenidone

KW - ly2109761

KW - imatinib

KW - sorafenib

KW - sunitinib

U2 - 10.1093/ecco-jcc/jju027.196

DO - 10.1093/ecco-jcc/jju027.196

M3 - Meeting Abstract

VL - 9

SP - s116

JO - Journal of Crohn's and Colitis

JF - Journal of Crohn's and Colitis

SN - 1873-9946

IS - suppl 1

ER -

ID: 22508167