Publication

In vitro and ex vivo anti-fibrotic effects of LY2109761, a small molecule inhibitor against TGF-β

Luangmonkong, T., Suriguga, S., Adhyatmika, A., Adlia, A., Oosterhuis, D., Suthisisang, C., de Jong, K. P., Mutsaers, H. A. M. & Olinga, P., 15-Sep-2018, In : Toxicology and Applied Pharmacology. 355, p. 127-137 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Luangmonkong, T., Suriguga, S., Adhyatmika, A., Adlia, A., Oosterhuis, D., Suthisisang, C., ... Olinga, P. (2018). In vitro and ex vivo anti-fibrotic effects of LY2109761, a small molecule inhibitor against TGF-β. Toxicology and Applied Pharmacology, 355, 127-137. https://doi.org/10.1016/j.taap.2018.07.001

Author

Luangmonkong, Theerut ; Suriguga, Su ; Adhyatmika, Adhyatmika ; Adlia, Amirah ; Oosterhuis, Dorenda ; Suthisisang, Chuthamanee ; de Jong, Koert P ; Mutsaers, Henricus A M ; Olinga, Peter. / In vitro and ex vivo anti-fibrotic effects of LY2109761, a small molecule inhibitor against TGF-β. In: Toxicology and Applied Pharmacology. 2018 ; Vol. 355. pp. 127-137.

Harvard

Luangmonkong, T, Suriguga, S, Adhyatmika, A, Adlia, A, Oosterhuis, D, Suthisisang, C, de Jong, KP, Mutsaers, HAM & Olinga, P 2018, 'In vitro and ex vivo anti-fibrotic effects of LY2109761, a small molecule inhibitor against TGF-β', Toxicology and Applied Pharmacology, vol. 355, pp. 127-137. https://doi.org/10.1016/j.taap.2018.07.001

Standard

In vitro and ex vivo anti-fibrotic effects of LY2109761, a small molecule inhibitor against TGF-β. / Luangmonkong, Theerut; Suriguga, Su; Adhyatmika, Adhyatmika; Adlia, Amirah; Oosterhuis, Dorenda; Suthisisang, Chuthamanee; de Jong, Koert P; Mutsaers, Henricus A M; Olinga, Peter.

In: Toxicology and Applied Pharmacology, Vol. 355, 15.09.2018, p. 127-137.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Luangmonkong T, Suriguga S, Adhyatmika A, Adlia A, Oosterhuis D, Suthisisang C et al. In vitro and ex vivo anti-fibrotic effects of LY2109761, a small molecule inhibitor against TGF-β. Toxicology and Applied Pharmacology. 2018 Sep 15;355:127-137. https://doi.org/10.1016/j.taap.2018.07.001


BibTeX

@article{c4265f894e7c453899522413604a5641,
title = "In vitro and ex vivo anti-fibrotic effects of LY2109761, a small molecule inhibitor against TGF-β",
abstract = "Fibrosis is a pathophysiological state characterized by the excessive formation/deposition of fibrous extracellular matrix. Transforming growth factor-beta (TGF-β) is a central profibrotic mediator, and targeting TGF-β is a promising strategy in the development of drugs for the treatment of fibrosis. Therefore, the effect of LY2109761, a small molecule inhibitor against TGF-β with targets beyond TGF-β signaling, on fibrogenesis was elucidated in vitro (HepG2 cells and LX-2 cells) and ex vivo (human and rat precision-cut liver slices). Our results displayed an anti-fibrotic effect of LY2109761, as it markedly down-regulated gene and protein expression of collagen type 1, as well as gene expression of the inhibitor of metalloproteinases 1. This effect on fibrosis markers was partially mediated by targeting TGF-β signaling, seeing that LY2109761 inhibited TGF-β1 gene expression and SMAD2 protein phosphorylation. Interestingly, particularly at a high concentration, LY2109761 decreased SMAD1 protein phosphorylation and gene expression of the inhibitor of DNA binding 1, which appeared to be TGF-β-independent effects. In conclusion, LY2109761 exhibited preclinical anti-fibrotic effects via both TGF-β-dependent and -independent pathways. These results illustrate that small molecule inhibitors directed against TGF-β could possibly influence numerous signaling pathways and thereby mitigate fibrogenesis.",
author = "Theerut Luangmonkong and Su Suriguga and Adhyatmika Adhyatmika and Amirah Adlia and Dorenda Oosterhuis and Chuthamanee Suthisisang and {de Jong}, {Koert P} and Mutsaers, {Henricus A M} and Peter Olinga",
note = "Copyright {\circledC} 2018 Elsevier Inc. All rights reserved.",
year = "2018",
month = "9",
day = "15",
doi = "10.1016/j.taap.2018.07.001",
language = "English",
volume = "355",
pages = "127--137",
journal = "Toxicology and Applied Pharmacology",
issn = "0041-008X",
publisher = "ACADEMIC PRESS INC ELSEVIER SCIENCE",

}

RIS

TY - JOUR

T1 - In vitro and ex vivo anti-fibrotic effects of LY2109761, a small molecule inhibitor against TGF-β

AU - Luangmonkong, Theerut

AU - Suriguga, Su

AU - Adhyatmika, Adhyatmika

AU - Adlia, Amirah

AU - Oosterhuis, Dorenda

AU - Suthisisang, Chuthamanee

AU - de Jong, Koert P

AU - Mutsaers, Henricus A M

AU - Olinga, Peter

N1 - Copyright © 2018 Elsevier Inc. All rights reserved.

PY - 2018/9/15

Y1 - 2018/9/15

N2 - Fibrosis is a pathophysiological state characterized by the excessive formation/deposition of fibrous extracellular matrix. Transforming growth factor-beta (TGF-β) is a central profibrotic mediator, and targeting TGF-β is a promising strategy in the development of drugs for the treatment of fibrosis. Therefore, the effect of LY2109761, a small molecule inhibitor against TGF-β with targets beyond TGF-β signaling, on fibrogenesis was elucidated in vitro (HepG2 cells and LX-2 cells) and ex vivo (human and rat precision-cut liver slices). Our results displayed an anti-fibrotic effect of LY2109761, as it markedly down-regulated gene and protein expression of collagen type 1, as well as gene expression of the inhibitor of metalloproteinases 1. This effect on fibrosis markers was partially mediated by targeting TGF-β signaling, seeing that LY2109761 inhibited TGF-β1 gene expression and SMAD2 protein phosphorylation. Interestingly, particularly at a high concentration, LY2109761 decreased SMAD1 protein phosphorylation and gene expression of the inhibitor of DNA binding 1, which appeared to be TGF-β-independent effects. In conclusion, LY2109761 exhibited preclinical anti-fibrotic effects via both TGF-β-dependent and -independent pathways. These results illustrate that small molecule inhibitors directed against TGF-β could possibly influence numerous signaling pathways and thereby mitigate fibrogenesis.

AB - Fibrosis is a pathophysiological state characterized by the excessive formation/deposition of fibrous extracellular matrix. Transforming growth factor-beta (TGF-β) is a central profibrotic mediator, and targeting TGF-β is a promising strategy in the development of drugs for the treatment of fibrosis. Therefore, the effect of LY2109761, a small molecule inhibitor against TGF-β with targets beyond TGF-β signaling, on fibrogenesis was elucidated in vitro (HepG2 cells and LX-2 cells) and ex vivo (human and rat precision-cut liver slices). Our results displayed an anti-fibrotic effect of LY2109761, as it markedly down-regulated gene and protein expression of collagen type 1, as well as gene expression of the inhibitor of metalloproteinases 1. This effect on fibrosis markers was partially mediated by targeting TGF-β signaling, seeing that LY2109761 inhibited TGF-β1 gene expression and SMAD2 protein phosphorylation. Interestingly, particularly at a high concentration, LY2109761 decreased SMAD1 protein phosphorylation and gene expression of the inhibitor of DNA binding 1, which appeared to be TGF-β-independent effects. In conclusion, LY2109761 exhibited preclinical anti-fibrotic effects via both TGF-β-dependent and -independent pathways. These results illustrate that small molecule inhibitors directed against TGF-β could possibly influence numerous signaling pathways and thereby mitigate fibrogenesis.

U2 - 10.1016/j.taap.2018.07.001

DO - 10.1016/j.taap.2018.07.001

M3 - Article

VL - 355

SP - 127

EP - 137

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

SN - 0041-008X

ER -

ID: 66881919