FGF10-FGFR2B Signaling Generates Basal Cells and Drives Alveolar Epithelial Regeneration by Bronchial Epithelial Stem Cells after Lung Injury
Summary: 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 str...
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Elsevier
2019-05-01
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Series: | Stem Cell Reports |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2213671119301250 |
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doaj-fcba214ffea4484dac67b28149cb14a9 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tingting Yuan Thomas Volckaert Elizabeth F. Redente Seantel Hopkins Kylie Klinkhammer Roxana Wasnick Cho-Ming Chao Jie Yuan Jin-San Zhang Changfu Yao Susan Majka Barry R. Stripp Andreas Günther David W.H. Riches Saverio Bellusci Victor J. Thannickal Stijn P. De Langhe |
spellingShingle |
Tingting Yuan Thomas Volckaert Elizabeth F. Redente Seantel Hopkins Kylie Klinkhammer Roxana Wasnick Cho-Ming Chao Jie Yuan Jin-San Zhang Changfu Yao Susan Majka Barry R. Stripp Andreas Günther David W.H. Riches Saverio Bellusci Victor J. Thannickal Stijn P. De Langhe FGF10-FGFR2B Signaling Generates Basal Cells and Drives Alveolar Epithelial Regeneration by Bronchial Epithelial Stem Cells after Lung Injury Stem Cell Reports |
author_facet |
Tingting Yuan Thomas Volckaert Elizabeth F. Redente Seantel Hopkins Kylie Klinkhammer Roxana Wasnick Cho-Ming Chao Jie Yuan Jin-San Zhang Changfu Yao Susan Majka Barry R. Stripp Andreas Günther David W.H. Riches Saverio Bellusci Victor J. Thannickal Stijn P. De Langhe |
author_sort |
Tingting Yuan |
title |
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_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_sort |
fgf10-fgfr2b signaling generates basal cells and drives alveolar epithelial regeneration by bronchial epithelial stem cells after lung injury |
publisher |
Elsevier |
series |
Stem Cell Reports |
issn |
2213-6711 |
publishDate |
2019-05-01 |
description |
Summary: 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. : FGF10-FGFR2B signaling in bronchial epithelial stem cells is critical to drive both alveolar epithelial regeneration and the development of honeycomb cysts after bleomycin injury. Overexpression of Fgf10 in bronchial epithelial stem cells enhances fibrosis resolution by favoring the more desirable outcome of alveolar epithelial regeneration over the development of pathologic honeycomb cysts. Keywords: lung stem cells, lung regeneration, lung fibrosis, Fgf signaling |
url |
http://www.sciencedirect.com/science/article/pii/S2213671119301250 |
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doaj-fcba214ffea4484dac67b28149cb14a92020-11-25T01:18:01ZengElsevierStem Cell Reports2213-67112019-05-0112510411055FGF10-FGFR2B Signaling Generates Basal Cells and Drives Alveolar Epithelial Regeneration by Bronchial Epithelial Stem Cells after Lung InjuryTingting Yuan0Thomas Volckaert1Elizabeth F. Redente2Seantel Hopkins3Kylie Klinkhammer4Roxana Wasnick5Cho-Ming Chao6Jie Yuan7Jin-San Zhang8Changfu Yao9Susan Majka10Barry R. Stripp11Andreas Günther12David W.H. Riches13Saverio Bellusci14Victor J. Thannickal15Stijn P. De Langhe16Department of Medicine, Division of Pulmonary, Allergy & Critical Care Medicine, University of Alabama at Birmingham, THT 422, 1720 2nd Avenue S., Birmingham, 35294-2182 AL, USADepartment of Medicine, Division of Pulmonary, Allergy & Critical Care Medicine, University of Alabama at Birmingham, THT 422, 1720 2nd Avenue S., Birmingham, 35294-2182 AL, USADepartment of Pediatrics, Division of Cell Biology, National Jewish Health, Denver, CO 80206, USA; Denver Veteran Affairs Medical Center, Denver, CO 80206, USADepartment of Medicine, Division of Pulmonary, Allergy & Critical Care Medicine, University of Alabama at Birmingham, THT 422, 1720 2nd Avenue S., Birmingham, 35294-2182 AL, USADepartment of Medicine, Division of Pulmonary, Allergy & Critical Care Medicine, University of Alabama at Birmingham, THT 422, 1720 2nd Avenue S., Birmingham, 35294-2182 AL, USAGerman Center for Lung Research, Excellence Cluster Cardio-Pulmonary System, Universities of Giessen and Marburg Lung Center, 35392 Giessen, GermanyGerman Center for Lung Research, Excellence Cluster Cardio-Pulmonary System, Universities of Giessen and Marburg Lung Center, 35392 Giessen, GermanyDepartment of Medicine, Division of Pulmonary, Allergy & Critical Care Medicine, University of Alabama at Birmingham, THT 422, 1720 2nd Avenue S., Birmingham, 35294-2182 AL, USASchool of Pharmaceutical Sciences, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325035, ChinaWomen's Guild Lung Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USADepartment of Medicine, National Jewish Health, Denver, CO 80206, USAWomen's Guild Lung Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USAGerman Center for Lung Research, Excellence Cluster Cardio-Pulmonary System, Universities of Giessen and Marburg Lung Center, 35392 Giessen, GermanyDepartment of Pediatrics, Division of Cell Biology, National Jewish Health, Denver, CO 80206, USA; Denver Veteran Affairs Medical Center, Denver, CO 80206, USAGerman Center for Lung Research, Excellence Cluster Cardio-Pulmonary System, Universities of Giessen and Marburg Lung Center, 35392 Giessen, GermanyDepartment of Medicine, Division of Pulmonary, Allergy & Critical Care Medicine, University of Alabama at Birmingham, THT 422, 1720 2nd Avenue S., Birmingham, 35294-2182 AL, USADepartment of Medicine, Division of Pulmonary, Allergy & Critical Care Medicine, University of Alabama at Birmingham, THT 422, 1720 2nd Avenue S., Birmingham, 35294-2182 AL, USA; Corresponding authorSummary: 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. : FGF10-FGFR2B signaling in bronchial epithelial stem cells is critical to drive both alveolar epithelial regeneration and the development of honeycomb cysts after bleomycin injury. Overexpression of Fgf10 in bronchial epithelial stem cells enhances fibrosis resolution by favoring the more desirable outcome of alveolar epithelial regeneration over the development of pathologic honeycomb cysts. Keywords: lung stem cells, lung regeneration, lung fibrosis, Fgf signalinghttp://www.sciencedirect.com/science/article/pii/S2213671119301250 |