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.
Department of Pediatrics, Division of Cell Biology, National Jewish Health, Denver, CO 80206, USA; Denver Veteran Affairs Medical Center, Denver, CO 80206, USA.
Stem Cell Reports. 2019 May 14;12(5):1041-1055. doi: 10.1016/j.stemcr.2019.04.003. Epub 2019 May 2.
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.
特发性肺纤维化是一种常见的间质性肺疾病，导致肺泡重塑和肺功能进行性丧失，原因是慢性肺泡损伤和呼吸上皮不能再生。组织学上，表达非典型近端气道上皮标志物的纤维化病变和蜂窝结构取代了肺泡结构，后者通常由肺泡型 1 (AT1) 和 AT2 细胞组成。支气管上皮干细胞 (BESCs) 可以在博来霉素介导的肺损伤后产生 AT2 和 AT1 细胞或蜂窝状囊肿。然而，人们对控制这种二元决策的因素知之甚少，也不知道这种决策是否可以逆转。在这里，我们报告说，BESCs 中 Fgfr2b 的失活会损害它们对博来霉素损伤后肺泡上皮再生和蜂窝囊肿的贡献。相比之下，BESCs 中 Fgf10 的过表达通过促进更理想的肺泡上皮再生结果而不是病理性蜂窝囊肿的发展，有利于纤维化的解决。
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