Comparative analysis of lysyl oxidase (like) family members in pulmonary fibrosis

Abstract Extracellular matrix (ECM) composition and stiffness are major driving forces for the development and persistence of fibrotic diseases. Lysyl oxidase (LOX) and LOX-like (LOXL) proteins play crucial roles in ECM remodeling due to their collagen crosslinking and intracellular functions. Here,...

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Autores principales:	Verena Aumiller, Benjamin Strobel, Merrit Romeike, Michael Schuler, Birgit E. Stierstorfer, Sebastian Kreuz
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f49ed3e8609443a9a3c9383cebe1ceb5
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spelling	oai:doaj.org-article:f49ed3e8609443a9a3c9383cebe1ceb52021-12-02T11:41:11ZComparative analysis of lysyl oxidase (like) family members in pulmonary fibrosis10.1038/s41598-017-00270-02045-2322https://doaj.org/article/f49ed3e8609443a9a3c9383cebe1ceb52017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00270-0https://doaj.org/toc/2045-2322Abstract Extracellular matrix (ECM) composition and stiffness are major driving forces for the development and persistence of fibrotic diseases. Lysyl oxidase (LOX) and LOX-like (LOXL) proteins play crucial roles in ECM remodeling due to their collagen crosslinking and intracellular functions. Here, we systematically investigated LOX/L expression in primary fibroblasts and epithelial cells under fibrotic conditions, Bleomycin (BLM) induced lung fibrosis and in human IPF tissue. Basal expression of all LOX/L family members was detected in epithelial cells and at higher levels in fibroblasts. Various pro-fibrotic stimuli broadly induced LOX/L expression in fibroblasts, whereas specific induction of LOXL2 and partially LOX was observed in epithelial cells. Immunohistochemical analysis of lung tissue from 14 IPF patients and healthy donors revealed strong induction of LOX and LOXL2 in bronchial and alveolar epithelium as well as fibroblastic foci. Using siRNA experiments we observed that LOXL2 and LOXL3 were crucial for fibroblast-to-myofibroblast transition (FMT). As FMT could only be reconstituted with an enzymatically active LOXL2 variant, we conclude that LOXL2 enzymatic function is crucial for fibroblast transdifferentiation. In summary, our study provides a comprehensive analysis of the LOX/L family in fibrotic lung disease and indicates prominent roles for LOXL2/3 in fibroblast activation and LOX/LOXL2 in IPF.Verena AumillerBenjamin StrobelMerrit RomeikeMichael SchulerBirgit E. StierstorferSebastian KreuzNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Verena Aumiller Benjamin Strobel Merrit Romeike Michael Schuler Birgit E. Stierstorfer Sebastian Kreuz Comparative analysis of lysyl oxidase (like) family members in pulmonary fibrosis
description	Abstract Extracellular matrix (ECM) composition and stiffness are major driving forces for the development and persistence of fibrotic diseases. Lysyl oxidase (LOX) and LOX-like (LOXL) proteins play crucial roles in ECM remodeling due to their collagen crosslinking and intracellular functions. Here, we systematically investigated LOX/L expression in primary fibroblasts and epithelial cells under fibrotic conditions, Bleomycin (BLM) induced lung fibrosis and in human IPF tissue. Basal expression of all LOX/L family members was detected in epithelial cells and at higher levels in fibroblasts. Various pro-fibrotic stimuli broadly induced LOX/L expression in fibroblasts, whereas specific induction of LOXL2 and partially LOX was observed in epithelial cells. Immunohistochemical analysis of lung tissue from 14 IPF patients and healthy donors revealed strong induction of LOX and LOXL2 in bronchial and alveolar epithelium as well as fibroblastic foci. Using siRNA experiments we observed that LOXL2 and LOXL3 were crucial for fibroblast-to-myofibroblast transition (FMT). As FMT could only be reconstituted with an enzymatically active LOXL2 variant, we conclude that LOXL2 enzymatic function is crucial for fibroblast transdifferentiation. In summary, our study provides a comprehensive analysis of the LOX/L family in fibrotic lung disease and indicates prominent roles for LOXL2/3 in fibroblast activation and LOX/LOXL2 in IPF.
format	article
author	Verena Aumiller Benjamin Strobel Merrit Romeike Michael Schuler Birgit E. Stierstorfer Sebastian Kreuz
author_facet	Verena Aumiller Benjamin Strobel Merrit Romeike Michael Schuler Birgit E. Stierstorfer Sebastian Kreuz
author_sort	Verena Aumiller
title	Comparative analysis of lysyl oxidase (like) family members in pulmonary fibrosis
title_short	Comparative analysis of lysyl oxidase (like) family members in pulmonary fibrosis
title_full	Comparative analysis of lysyl oxidase (like) family members in pulmonary fibrosis
title_fullStr	Comparative analysis of lysyl oxidase (like) family members in pulmonary fibrosis
title_full_unstemmed	Comparative analysis of lysyl oxidase (like) family members in pulmonary fibrosis
title_sort	comparative analysis of lysyl oxidase (like) family members in pulmonary fibrosis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f49ed3e8609443a9a3c9383cebe1ceb5
work_keys_str_mv	AT verenaaumiller comparativeanalysisoflysyloxidaselikefamilymembersinpulmonaryfibrosis AT benjaminstrobel comparativeanalysisoflysyloxidaselikefamilymembersinpulmonaryfibrosis AT merritromeike comparativeanalysisoflysyloxidaselikefamilymembersinpulmonaryfibrosis AT michaelschuler comparativeanalysisoflysyloxidaselikefamilymembersinpulmonaryfibrosis AT birgitestierstorfer comparativeanalysisoflysyloxidaselikefamilymembersinpulmonaryfibrosis AT sebastiankreuz comparativeanalysisoflysyloxidaselikefamilymembersinpulmonaryfibrosis
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Comparative analysis of lysyl oxidase (like) family members in pulmonary fibrosis

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