Patho-mechanisms of the origins of bronchopulmonary dysplasia

Abstract

Bronchopulmonary dysplasia (BPD) continues to be one of the most common complications of prematurity, despite significant advancement in neonatology over the last couple of decades. The new BPD is characterized histopathologically by impaired lung alveolarization and dysregulated vascularization. With the increased survival of extremely preterm infants, the risk for the development of BPD remains high, emphasizing the continued need to understand the patho-mechanisms that play a role in the development of this disease. This brief review summarizes recent advances in our understanding of the maldevelopment of the premature lung, highlighting recent research in pathways of oxidative stress-related lung injury, the role of placental insufficiency, growth factor signaling, the extracellular matrix, and microRNAs.

Keywords: Chronic lung disease; Growth factors; Hyperoxia; Placenta; Preterm lung; miRNA.

Fig. 1

Exposure to hyperoxia leads to production of reactive oxygen species (ROS) that leads to an exaggerated inflammatory response, and releases cytokines and other molecular mediators. Subsequently, this causes abnormal responses of angiogenic factors, growth factor signaling, abnormal matrix protein formation, mitochondrial dysfunction, cell cycle arrest, and cell death. This, in turn, causes impaired alveolarization and dysregulated vasculature which is pathognomic of bronchopulmonary dysplasia (BPD). BAX, bcl-2 like protein; NADPH: nicotinamide adenine dinucleotide phosphate; TGFβ, transforming growth factor β; CTGF, connective tissue growth factor; PDGF, platelet-derived growth factor; KGF, keratinocyte growth factor; VEGF, vascular endothelial growth factor; Ang-2, angiopoietin 2; Cyt c, cytochrome c; IFNγ, interferon gamma; NF-κB, nuclear factor-kappa B; pkB, protein kinase B