Publication

Design of a Gene Panel to Expose the Versatile Role of Hepatic Stellate Cells in Human Liver Fibrosis

van Dijk, F., Hazelhoff, C. M., Post, E., Prins, G. G. H., Rombouts, K., Poelstra, K., Olinga, P. & Beljaars, L., Mar-2020, In : Pharmaceutics. 12, 3, 15 p., 278.

Research output: Contribution to journalArticleAcademicpeer-review

APA

van Dijk, F., Hazelhoff, C. M., Post, E., Prins, G. G. H., Rombouts, K., Poelstra, K., Olinga, P., & Beljaars, L. (2020). Design of a Gene Panel to Expose the Versatile Role of Hepatic Stellate Cells in Human Liver Fibrosis. Pharmaceutics, 12(3), [278]. https://doi.org/10.3390/pharmaceutics12030278

Author

van Dijk, Fransien ; Hazelhoff, Christa M. ; Post, Eduard ; Prins, Gerian G. H. ; Rombouts, Krista ; Poelstra, Klaas ; Olinga, Peter ; Beljaars, Leonie. / Design of a Gene Panel to Expose the Versatile Role of Hepatic Stellate Cells in Human Liver Fibrosis. In: Pharmaceutics. 2020 ; Vol. 12, No. 3.

Harvard

van Dijk, F, Hazelhoff, CM, Post, E, Prins, GGH, Rombouts, K, Poelstra, K, Olinga, P & Beljaars, L 2020, 'Design of a Gene Panel to Expose the Versatile Role of Hepatic Stellate Cells in Human Liver Fibrosis', Pharmaceutics, vol. 12, no. 3, 278. https://doi.org/10.3390/pharmaceutics12030278

Standard

Design of a Gene Panel to Expose the Versatile Role of Hepatic Stellate Cells in Human Liver Fibrosis. / van Dijk, Fransien; Hazelhoff, Christa M.; Post, Eduard; Prins, Gerian G. H.; Rombouts, Krista; Poelstra, Klaas; Olinga, Peter; Beljaars, Leonie.

In: Pharmaceutics, Vol. 12, No. 3, 278, 03.2020.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

van Dijk F, Hazelhoff CM, Post E, Prins GGH, Rombouts K, Poelstra K et al. Design of a Gene Panel to Expose the Versatile Role of Hepatic Stellate Cells in Human Liver Fibrosis. Pharmaceutics. 2020 Mar;12(3). 278. https://doi.org/10.3390/pharmaceutics12030278


BibTeX

@article{0d6ed2043ebe4315a3ee8872118e55f1,
title = "Design of a Gene Panel to Expose the Versatile Role of Hepatic Stellate Cells in Human Liver Fibrosis",
abstract = "The pivotal cell involved in the pathogenesis of liver fibrosis, i.e., the activated hepatic stellate cell (HSC), has a wide range of activities during the initiation, progression and even regression of the disease. These HSC-related activities encompass cellular activation, matrix synthesis and degradation, proliferation, contraction, chemotaxis and inflammatory signaling. When determining the in vitro and in vivo effectivity of novel antifibrotic therapies, the readout is currently mainly based on gene and protein levels of α-smooth muscle actin (α-SMA) and the fibrillar collagens (type I and III). We advocate for a more comprehensive approach in addition to these markers when screening potential antifibrotic drugs that interfere with HSCs. Therefore, we aimed to develop a gene panel for human in vitro and ex vivo drug screening models, addressing each of the HSC-activities with at least one gene, comprising, in total, 16 genes. We determined the gene expression in various human stellate cells, ranging from primary cells to cell lines with an HSC-origin, and human liver slices and stimulated them with two key profibrotic factors, i.e., transforming growth factor β (TGFβ) or platelet-derived growth factor BB (PDGF-BB). We demonstrated that freshly isolated HSCs showed the strongest and highest variety of responses to these profibrotic stimuli, in particular following PDGF-BB stimulation, while cell lines were limited in their responses. Moreover, we verified these gene expression profiles in human precision-cut liver slices and showed similarities with the TGFβ- and PDGF-BB-related fibrotic responses, as observed in the primary HSCs. With this study, we encourage researchers to get off the beaten track when testing antifibrotic compounds by including more HSC-related markers in their future work. This way, potential compounds will be screened more extensively, which might increase the likelihood of developing effective antifibrotic drugs.",
keywords = "PRECISION-CUT LIVER, ACTIVATION, MECHANISMS, PHENOTYPE, DISEASE, SLICES, SIGNAL",
author = "{van Dijk}, Fransien and Hazelhoff, {Christa M.} and Eduard Post and Prins, {Gerian G. H.} and Krista Rombouts and Klaas Poelstra and Peter Olinga and Leonie Beljaars",
year = "2020",
month = mar,
doi = "10.3390/pharmaceutics12030278",
language = "English",
volume = "12",
journal = "Pharmaceutics",
issn = "1999-4923",
publisher = "MDPI AG",
number = "3",

}

RIS

TY - JOUR

T1 - Design of a Gene Panel to Expose the Versatile Role of Hepatic Stellate Cells in Human Liver Fibrosis

AU - van Dijk, Fransien

AU - Hazelhoff, Christa M.

AU - Post, Eduard

AU - Prins, Gerian G. H.

AU - Rombouts, Krista

AU - Poelstra, Klaas

AU - Olinga, Peter

AU - Beljaars, Leonie

PY - 2020/3

Y1 - 2020/3

N2 - The pivotal cell involved in the pathogenesis of liver fibrosis, i.e., the activated hepatic stellate cell (HSC), has a wide range of activities during the initiation, progression and even regression of the disease. These HSC-related activities encompass cellular activation, matrix synthesis and degradation, proliferation, contraction, chemotaxis and inflammatory signaling. When determining the in vitro and in vivo effectivity of novel antifibrotic therapies, the readout is currently mainly based on gene and protein levels of α-smooth muscle actin (α-SMA) and the fibrillar collagens (type I and III). We advocate for a more comprehensive approach in addition to these markers when screening potential antifibrotic drugs that interfere with HSCs. Therefore, we aimed to develop a gene panel for human in vitro and ex vivo drug screening models, addressing each of the HSC-activities with at least one gene, comprising, in total, 16 genes. We determined the gene expression in various human stellate cells, ranging from primary cells to cell lines with an HSC-origin, and human liver slices and stimulated them with two key profibrotic factors, i.e., transforming growth factor β (TGFβ) or platelet-derived growth factor BB (PDGF-BB). We demonstrated that freshly isolated HSCs showed the strongest and highest variety of responses to these profibrotic stimuli, in particular following PDGF-BB stimulation, while cell lines were limited in their responses. Moreover, we verified these gene expression profiles in human precision-cut liver slices and showed similarities with the TGFβ- and PDGF-BB-related fibrotic responses, as observed in the primary HSCs. With this study, we encourage researchers to get off the beaten track when testing antifibrotic compounds by including more HSC-related markers in their future work. This way, potential compounds will be screened more extensively, which might increase the likelihood of developing effective antifibrotic drugs.

AB - The pivotal cell involved in the pathogenesis of liver fibrosis, i.e., the activated hepatic stellate cell (HSC), has a wide range of activities during the initiation, progression and even regression of the disease. These HSC-related activities encompass cellular activation, matrix synthesis and degradation, proliferation, contraction, chemotaxis and inflammatory signaling. When determining the in vitro and in vivo effectivity of novel antifibrotic therapies, the readout is currently mainly based on gene and protein levels of α-smooth muscle actin (α-SMA) and the fibrillar collagens (type I and III). We advocate for a more comprehensive approach in addition to these markers when screening potential antifibrotic drugs that interfere with HSCs. Therefore, we aimed to develop a gene panel for human in vitro and ex vivo drug screening models, addressing each of the HSC-activities with at least one gene, comprising, in total, 16 genes. We determined the gene expression in various human stellate cells, ranging from primary cells to cell lines with an HSC-origin, and human liver slices and stimulated them with two key profibrotic factors, i.e., transforming growth factor β (TGFβ) or platelet-derived growth factor BB (PDGF-BB). We demonstrated that freshly isolated HSCs showed the strongest and highest variety of responses to these profibrotic stimuli, in particular following PDGF-BB stimulation, while cell lines were limited in their responses. Moreover, we verified these gene expression profiles in human precision-cut liver slices and showed similarities with the TGFβ- and PDGF-BB-related fibrotic responses, as observed in the primary HSCs. With this study, we encourage researchers to get off the beaten track when testing antifibrotic compounds by including more HSC-related markers in their future work. This way, potential compounds will be screened more extensively, which might increase the likelihood of developing effective antifibrotic drugs.

KW - PRECISION-CUT LIVER

KW - ACTIVATION

KW - MECHANISMS

KW - PHENOTYPE

KW - DISEASE

KW - SLICES

KW - SIGNAL

U2 - 10.3390/pharmaceutics12030278

DO - 10.3390/pharmaceutics12030278

M3 - Article

C2 - 32244897

VL - 12

JO - Pharmaceutics

JF - Pharmaceutics

SN - 1999-4923

IS - 3

M1 - 278

ER -

ID: 121945329