Exploring organ-specific features of fibrogenesis using murine precision-cut tissue slices

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Exploring organ-specific features of fibrogenesis using murine precision-cut tissue slices. / Bigaeva, Emilia; Gore, Emilia; Mutsaers, Henricus A.M.; Oosterhuis, Dorenda; Kim, Yong Ook; Schuppan, Detlef; Bank, Ruud A.; Boersema, Miriam; Olinga, Peter.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1866, No. 1, 165582, 01.2020.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Bigaeva, E, Gore, E, Mutsaers, HAM, Oosterhuis, D, Kim, YO, Schuppan, D, Bank, RA, Boersema, M & Olinga, P 2020, 'Exploring organ-specific features of fibrogenesis using murine precision-cut tissue slices', Biochimica et Biophysica Acta - Molecular Basis of Disease, vol. 1866, no. 1, 165582. https://doi.org/10.1016/j.bbadis.2019.165582

APA

Bigaeva, E., Gore, E., Mutsaers, H. A. M., Oosterhuis, D., Kim, Y. O., Schuppan, D., Bank, R. A., Boersema, M., & Olinga, P. (2020). Exploring organ-specific features of fibrogenesis using murine precision-cut tissue slices. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1866(1), [165582]. https://doi.org/10.1016/j.bbadis.2019.165582

CBE

Bigaeva E, Gore E, Mutsaers HAM, Oosterhuis D, Kim YO, Schuppan D, Bank RA, Boersema M, Olinga P. 2020. Exploring organ-specific features of fibrogenesis using murine precision-cut tissue slices. Biochimica et Biophysica Acta - Molecular Basis of Disease. 1866(1):Article 165582. https://doi.org/10.1016/j.bbadis.2019.165582

MLA

Bigaeva, Emilia et al. "Exploring organ-specific features of fibrogenesis using murine precision-cut tissue slices". Biochimica et Biophysica Acta - Molecular Basis of Disease. 2020. 1866(1). https://doi.org/10.1016/j.bbadis.2019.165582

Vancouver

Bigaeva E, Gore E, Mutsaers HAM, Oosterhuis D, Kim YO, Schuppan D et al. Exploring organ-specific features of fibrogenesis using murine precision-cut tissue slices. Biochimica et Biophysica Acta - Molecular Basis of Disease. 2020 Jan;1866(1). 165582. https://doi.org/10.1016/j.bbadis.2019.165582

Author

Bigaeva, Emilia ; Gore, Emilia ; Mutsaers, Henricus A.M. ; Oosterhuis, Dorenda ; Kim, Yong Ook ; Schuppan, Detlef ; Bank, Ruud A. ; Boersema, Miriam ; Olinga, Peter. / Exploring organ-specific features of fibrogenesis using murine precision-cut tissue slices. In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2020 ; Vol. 1866, No. 1.

Bibtex

@article{7612bd57aac8491c813d7a199375c11f,
title = "Exploring organ-specific features of fibrogenesis using murine precision-cut tissue slices",
abstract = "Fibrosis is the hallmark of pathologic tissue remodelling in most chronic diseases. Despite advances in our understanding of the mechanisms of fibrosis, it remains uncured. Fibrogenic processes share conserved core cellular and molecular pathways across organs. In this study, we aimed to elucidate shared and organ-specific features of fibrosis using murine precision-cut tissue slices (PCTS) prepared from small intestine, liver and kidneys. PCTS displayed substantial differences in their baseline gene expression profiles: 70% of the extracellular matrix (ECM)-related genes were differentially expressed across the organs. Culture for 48 h induced significant changes in ECM regulation and triggered the onset of fibrogenesis in all PCTS in organ-specific manner. TGFβ signalling was activated during 48 h culture in all PCTS. However, the degree of its involvement varied: both canonical and non-canonical TGFβ pathways were activated in liver and kidney slices, while only canonical, Smad-dependent, cascade was involved in intestinal slices. The treatment with galunisertib blocked the TGFβRI/SMAD2 signalling in all PCTS, but attenuated culture-induced dysregulation of ECM homeostasis and mitigated the onset of fibrogenesis with organ-specificity. In conclusion, regardless the many common features in pathophysiology of organ fibrosis, PCTS displayed diversity in culture-induced responses and in response to the treatment with TGFβRI kinase inhibitor galunisertib, even though it targets a core fibrosis pathway. A clear understanding of the common and organ-specific features of fibrosis is the basis for developing novel antifibrotic therapies.",
keywords = "Collagen, Extracellular matrix, Fibrosis, Precision-cut tissue slices, SMAD2, TGFβ",
author = "Emilia Bigaeva and Emilia Gore and Mutsaers, {Henricus A.M.} and Dorenda Oosterhuis and Kim, {Yong Ook} and Detlef Schuppan and Bank, {Ruud A.} and Miriam Boersema and Peter Olinga",
year = "2020",
month = jan,
doi = "10.1016/j.bbadis.2019.165582",
language = "English",
volume = "1866",
journal = "B B A - Molecular Basis of Disease",
issn = "0925-4439",
publisher = "Elsevier BV",
number = "1",

}

RIS

TY - JOUR

T1 - Exploring organ-specific features of fibrogenesis using murine precision-cut tissue slices

AU - Bigaeva, Emilia

AU - Gore, Emilia

AU - Mutsaers, Henricus A.M.

AU - Oosterhuis, Dorenda

AU - Kim, Yong Ook

AU - Schuppan, Detlef

AU - Bank, Ruud A.

AU - Boersema, Miriam

AU - Olinga, Peter

PY - 2020/1

Y1 - 2020/1

N2 - Fibrosis is the hallmark of pathologic tissue remodelling in most chronic diseases. Despite advances in our understanding of the mechanisms of fibrosis, it remains uncured. Fibrogenic processes share conserved core cellular and molecular pathways across organs. In this study, we aimed to elucidate shared and organ-specific features of fibrosis using murine precision-cut tissue slices (PCTS) prepared from small intestine, liver and kidneys. PCTS displayed substantial differences in their baseline gene expression profiles: 70% of the extracellular matrix (ECM)-related genes were differentially expressed across the organs. Culture for 48 h induced significant changes in ECM regulation and triggered the onset of fibrogenesis in all PCTS in organ-specific manner. TGFβ signalling was activated during 48 h culture in all PCTS. However, the degree of its involvement varied: both canonical and non-canonical TGFβ pathways were activated in liver and kidney slices, while only canonical, Smad-dependent, cascade was involved in intestinal slices. The treatment with galunisertib blocked the TGFβRI/SMAD2 signalling in all PCTS, but attenuated culture-induced dysregulation of ECM homeostasis and mitigated the onset of fibrogenesis with organ-specificity. In conclusion, regardless the many common features in pathophysiology of organ fibrosis, PCTS displayed diversity in culture-induced responses and in response to the treatment with TGFβRI kinase inhibitor galunisertib, even though it targets a core fibrosis pathway. A clear understanding of the common and organ-specific features of fibrosis is the basis for developing novel antifibrotic therapies.

AB - Fibrosis is the hallmark of pathologic tissue remodelling in most chronic diseases. Despite advances in our understanding of the mechanisms of fibrosis, it remains uncured. Fibrogenic processes share conserved core cellular and molecular pathways across organs. In this study, we aimed to elucidate shared and organ-specific features of fibrosis using murine precision-cut tissue slices (PCTS) prepared from small intestine, liver and kidneys. PCTS displayed substantial differences in their baseline gene expression profiles: 70% of the extracellular matrix (ECM)-related genes were differentially expressed across the organs. Culture for 48 h induced significant changes in ECM regulation and triggered the onset of fibrogenesis in all PCTS in organ-specific manner. TGFβ signalling was activated during 48 h culture in all PCTS. However, the degree of its involvement varied: both canonical and non-canonical TGFβ pathways were activated in liver and kidney slices, while only canonical, Smad-dependent, cascade was involved in intestinal slices. The treatment with galunisertib blocked the TGFβRI/SMAD2 signalling in all PCTS, but attenuated culture-induced dysregulation of ECM homeostasis and mitigated the onset of fibrogenesis with organ-specificity. In conclusion, regardless the many common features in pathophysiology of organ fibrosis, PCTS displayed diversity in culture-induced responses and in response to the treatment with TGFβRI kinase inhibitor galunisertib, even though it targets a core fibrosis pathway. A clear understanding of the common and organ-specific features of fibrosis is the basis for developing novel antifibrotic therapies.

KW - Collagen

KW - Extracellular matrix

KW - Fibrosis

KW - Precision-cut tissue slices

KW - SMAD2

KW - TGFβ

UR - http://www.scopus.com/inward/record.url?scp=85074779249&partnerID=8YFLogxK

U2 - 10.1016/j.bbadis.2019.165582

DO - 10.1016/j.bbadis.2019.165582

M3 - Journal article

C2 - 31676376

AN - SCOPUS:85074779249

VL - 1866

JO - B B A - Molecular Basis of Disease

JF - B B A - Molecular Basis of Disease

SN - 0925-4439

IS - 1

M1 - 165582

ER -