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FGF10-FGFR2B Signaling Generates Basal Cells and Drives Alveolar Epithelial Regeneration by Bronchial Epithelial Stem Cells after Lung Injury

Idiopathic pulmonary fibrosis is a common form of interstitial lung disease resulting in alveolar remodeling and progressive loss of pulmonary function because of chronic alveolar injury and failure to regenerate the respiratory epithelium. Histologically, fibrotic lesions and honeycomb structures e...

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Autores principales: Yuan, Tingting, Volckaert, Thomas, Redente, Elizabeth F., Hopkins, Seantel, Klinkhammer, Kylie, Wasnick, Roxana, Chao, Cho-Ming, Yuan, Jie, Zhang, Jin-San, Yao, Changfu, Majka, Susan, Stripp, Barry R., Günther, Andreas, Riches, David W.H., Bellusci, Saverio, Thannickal, Victor J., De Langhe, Stijn P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524168/
https://www.ncbi.nlm.nih.gov/pubmed/31056475
http://dx.doi.org/10.1016/j.stemcr.2019.04.003
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author Yuan, Tingting
Volckaert, Thomas
Redente, Elizabeth F.
Hopkins, Seantel
Klinkhammer, Kylie
Wasnick, Roxana
Chao, Cho-Ming
Yuan, Jie
Zhang, Jin-San
Yao, Changfu
Majka, Susan
Stripp, Barry R.
Günther, Andreas
Riches, David W.H.
Bellusci, Saverio
Thannickal, Victor J.
De Langhe, Stijn P.
author_facet Yuan, Tingting
Volckaert, Thomas
Redente, Elizabeth F.
Hopkins, Seantel
Klinkhammer, Kylie
Wasnick, Roxana
Chao, Cho-Ming
Yuan, Jie
Zhang, Jin-San
Yao, Changfu
Majka, Susan
Stripp, Barry R.
Günther, Andreas
Riches, David W.H.
Bellusci, Saverio
Thannickal, Victor J.
De Langhe, Stijn P.
author_sort Yuan, Tingting
collection PubMed
description Idiopathic pulmonary fibrosis is a common form of interstitial lung disease resulting in alveolar remodeling and progressive loss of pulmonary function because of chronic alveolar injury and failure to regenerate the respiratory epithelium. Histologically, fibrotic lesions and honeycomb structures expressing atypical proximal airway epithelial markers replace alveolar structures, the latter normally lined by alveolar type 1 (AT1) and AT2 cells. Bronchial epithelial stem cells (BESCs) can give rise to AT2 and AT1 cells or honeycomb cysts following bleomycin-mediated lung injury. However, little is known about what controls this binary decision or whether this decision can be reversed. Here we report that inactivation of Fgfr2b in BESCs impairs their contribution to both alveolar epithelial regeneration and honeycomb cysts after bleomycin injury. By contrast overexpression of Fgf10 in BESCs enhances fibrosis resolution by favoring the more desirable outcome of alveolar epithelial regeneration over the development of pathologic honeycomb cysts.
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spelling pubmed-65241682019-05-24 FGF10-FGFR2B Signaling Generates Basal Cells and Drives Alveolar Epithelial Regeneration by Bronchial Epithelial Stem Cells after Lung Injury Yuan, Tingting Volckaert, Thomas Redente, Elizabeth F. Hopkins, Seantel Klinkhammer, Kylie Wasnick, Roxana Chao, Cho-Ming Yuan, Jie Zhang, Jin-San Yao, Changfu Majka, Susan Stripp, Barry R. Günther, Andreas Riches, David W.H. Bellusci, Saverio Thannickal, Victor J. De Langhe, Stijn P. Stem Cell Reports Article Idiopathic pulmonary fibrosis is a common form of interstitial lung disease resulting in alveolar remodeling and progressive loss of pulmonary function because of chronic alveolar injury and failure to regenerate the respiratory epithelium. Histologically, fibrotic lesions and honeycomb structures expressing atypical proximal airway epithelial markers replace alveolar structures, the latter normally lined by alveolar type 1 (AT1) and AT2 cells. Bronchial epithelial stem cells (BESCs) can give rise to AT2 and AT1 cells or honeycomb cysts following bleomycin-mediated lung injury. However, little is known about what controls this binary decision or whether this decision can be reversed. Here we report that inactivation of Fgfr2b in BESCs impairs their contribution to both alveolar epithelial regeneration and honeycomb cysts after bleomycin injury. By contrast overexpression of Fgf10 in BESCs enhances fibrosis resolution by favoring the more desirable outcome of alveolar epithelial regeneration over the development of pathologic honeycomb cysts. Elsevier 2019-05-02 /pmc/articles/PMC6524168/ /pubmed/31056475 http://dx.doi.org/10.1016/j.stemcr.2019.04.003 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Yuan, Tingting
Volckaert, Thomas
Redente, Elizabeth F.
Hopkins, Seantel
Klinkhammer, Kylie
Wasnick, Roxana
Chao, Cho-Ming
Yuan, Jie
Zhang, Jin-San
Yao, Changfu
Majka, Susan
Stripp, Barry R.
Günther, Andreas
Riches, David W.H.
Bellusci, Saverio
Thannickal, Victor J.
De Langhe, Stijn P.
FGF10-FGFR2B Signaling Generates Basal Cells and Drives Alveolar Epithelial Regeneration by Bronchial Epithelial Stem Cells after Lung Injury
title FGF10-FGFR2B Signaling Generates Basal Cells and Drives Alveolar Epithelial Regeneration by Bronchial Epithelial Stem Cells after Lung Injury
title_full FGF10-FGFR2B Signaling Generates Basal Cells and Drives Alveolar Epithelial Regeneration by Bronchial Epithelial Stem Cells after Lung Injury
title_fullStr FGF10-FGFR2B Signaling Generates Basal Cells and Drives Alveolar Epithelial Regeneration by Bronchial Epithelial Stem Cells after Lung Injury
title_full_unstemmed FGF10-FGFR2B Signaling Generates Basal Cells and Drives Alveolar Epithelial Regeneration by Bronchial Epithelial Stem Cells after Lung Injury
title_short FGF10-FGFR2B Signaling Generates Basal Cells and Drives Alveolar Epithelial Regeneration by Bronchial Epithelial Stem Cells after Lung Injury
title_sort fgf10-fgfr2b signaling generates basal cells and drives alveolar epithelial regeneration by bronchial epithelial stem cells after lung injury
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524168/
https://www.ncbi.nlm.nih.gov/pubmed/31056475
http://dx.doi.org/10.1016/j.stemcr.2019.04.003
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