Abstract
Bronchopulmonary dysplasia (BPD) is one of the most common chronic lung diseases in infants caused by pre- and/or postnatal lung injury. BPD is characterized by arrested alveolarization and vascularization due to extracellular matrix remodeling, inflammation, and impaired growth factor signaling. WNT signaling is a critical pathway for normal lung development, and its altered signaling has been shown to be involved in the onset and progression of incurable chronic lung diseases in adulthood, such as chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF). In this review, we summarize the impact of WNT signaling on different stages of lung development and its potential contribution to developmental lung diseases, especially BPD, and chronic lung diseases in adulthood.
Highlights
Bronchopulmonary dysplasia (BPD) is one of the most common chronic lung diseases in infants
“Old” or “classical” BPD was first defined by Northway et al in 1967 as structural lung damage and subsequent appearance of parenchymal fibrosis caused by prolonged hyperoxia and ventilator-associated lung injury during the saccular to alveolar stage of lung development [1]
We focus on the potential role of WNT signaling in lung development and perinatal lung disease, with a focus on BPD, as a disease of impaired alveolarization/vascularization, and discuss the potential link between perinatal and adult chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF)
Summary
Bronchopulmonary dysplasia (BPD) is one of the most common chronic lung diseases in infants. Embryonic lung development starts as early as E9.5 (equivalent to 4 weeks in human gestation), with tightly coordinated epithelial and mesenchymal differentiation processes, and is completed postnatally At this time point, Nkx2.1, a critical homeodomain-containing transcription factor for initial respiratory specification, is expressed within endoderm progenitors in the anterior foregut [21]. Β-Catenin in normal lung development Studies modulating the major effector protein of canonical WNT signaling, β-catenin, revealed that both epithelial and mesenchymal β-catenin is required for the onset of lung specification and the proximal-distal patterning of branching morphogenesis: deletion of β-catenin in the foregut leads to the loss of Nkx2.1 expression and the absence of both the trachea and lung due to a lack of respiratory lineage initiation [27, 38]. APC knockout fetus shows severe lung hemorrhage in E14.5 and dies in E15.5, with condensed mesenchymal cells around epithelial tubes in the lung
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