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RANKL confers protection against cell death in precision-cut lung slices

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally and constitutes a major health problem. The disease is characterized by airflow obstructions due to chronic bronchitis and/or emphysema. Emerging evidence suggests that COPD is the result of impaired epithelial...

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Autores principales: Ruigrok, M. J. R., Roest, M. A. P., Frijlink, H. W., Olinga, P., Hinrichs, W. L. J., Melgert, B. N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9659591/
https://www.ncbi.nlm.nih.gov/pubmed/36388105
http://dx.doi.org/10.3389/fphys.2022.1029697
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author Ruigrok, M. J. R.
Roest, M. A. P.
Frijlink, H. W.
Olinga, P.
Hinrichs, W. L. J.
Melgert, B. N.
author_facet Ruigrok, M. J. R.
Roest, M. A. P.
Frijlink, H. W.
Olinga, P.
Hinrichs, W. L. J.
Melgert, B. N.
author_sort Ruigrok, M. J. R.
collection PubMed
description Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally and constitutes a major health problem. The disease is characterized by airflow obstructions due to chronic bronchitis and/or emphysema. Emerging evidence suggests that COPD is the result of impaired epithelial repair. Motivated by the need for more effective treatments, we studied whether receptor activator of nuclear factor κ-Β ligand (RANKL) contributed to epithelial repair, as this protein has been implicated in epithelial regeneration of breast and thymus. To do so, we used precision-cut lung slices prepared from mouse tissue—viable explants that can be cultured ex vivo for up to a few days while retaining features of lung tissue. Slices were cultured with 10, 100, or 500 ng/ml of mouse RANKL for 24 h. We first found RANKL activated nuclear factor κ-Β signaling, which is involved in cellular stress responses, without affecting the general viability of slices. Cell proliferation, however, was not altered by RANKL treatment. Interestingly, RANKL did reduce cell death, as revealed by TUNEL stainings and profiling of apoptosis-related proteins, indicating that it contributes to repair by conferring protection against cell death. This study improves our understanding of lung repair and could create new opportunities for developing COPD treatments.
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spelling pubmed-96595912022-11-15 RANKL confers protection against cell death in precision-cut lung slices Ruigrok, M. J. R. Roest, M. A. P. Frijlink, H. W. Olinga, P. Hinrichs, W. L. J. Melgert, B. N. Front Physiol Physiology Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally and constitutes a major health problem. The disease is characterized by airflow obstructions due to chronic bronchitis and/or emphysema. Emerging evidence suggests that COPD is the result of impaired epithelial repair. Motivated by the need for more effective treatments, we studied whether receptor activator of nuclear factor κ-Β ligand (RANKL) contributed to epithelial repair, as this protein has been implicated in epithelial regeneration of breast and thymus. To do so, we used precision-cut lung slices prepared from mouse tissue—viable explants that can be cultured ex vivo for up to a few days while retaining features of lung tissue. Slices were cultured with 10, 100, or 500 ng/ml of mouse RANKL for 24 h. We first found RANKL activated nuclear factor κ-Β signaling, which is involved in cellular stress responses, without affecting the general viability of slices. Cell proliferation, however, was not altered by RANKL treatment. Interestingly, RANKL did reduce cell death, as revealed by TUNEL stainings and profiling of apoptosis-related proteins, indicating that it contributes to repair by conferring protection against cell death. This study improves our understanding of lung repair and could create new opportunities for developing COPD treatments. Frontiers Media S.A. 2022-10-31 /pmc/articles/PMC9659591/ /pubmed/36388105 http://dx.doi.org/10.3389/fphys.2022.1029697 Text en Copyright © 2022 Ruigrok, Roest, Frijlink, Olinga, Hinrichs and Melgert. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Ruigrok, M. J. R.
Roest, M. A. P.
Frijlink, H. W.
Olinga, P.
Hinrichs, W. L. J.
Melgert, B. N.
RANKL confers protection against cell death in precision-cut lung slices
title RANKL confers protection against cell death in precision-cut lung slices
title_full RANKL confers protection against cell death in precision-cut lung slices
title_fullStr RANKL confers protection against cell death in precision-cut lung slices
title_full_unstemmed RANKL confers protection against cell death in precision-cut lung slices
title_short RANKL confers protection against cell death in precision-cut lung slices
title_sort rankl confers protection against cell death in precision-cut lung slices
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9659591/
https://www.ncbi.nlm.nih.gov/pubmed/36388105
http://dx.doi.org/10.3389/fphys.2022.1029697
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