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Stem Cell Reports. 2019 May 14;12(5):1041-1055. doi: 10.1016/j.stemcr.2019.04.003. Epub 2019 May 2.

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

Author information

1
Department 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.
2
Department of Pediatrics, Division of Cell Biology, National Jewish Health, Denver, CO 80206, USA; Denver Veteran Affairs Medical Center, Denver, CO 80206, USA.
3
German Center for Lung Research, Excellence Cluster Cardio-Pulmonary System, Universities of Giessen and Marburg Lung Center, 35392 Giessen, Germany.
4
School of Pharmaceutical Sciences, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
5
Women's Guild Lung Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
6
Department of Medicine, National Jewish Health, Denver, CO 80206, USA.
7
Department 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. Electronic address: sdelanghe@uabmc.edu.

Abstract

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.

KEYWORDS:

Fgf signaling; lung fibrosis; lung regeneration; lung stem cells

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