Proteoglycans and Hyaluronan in Normal and Aberrant Lung Development

ABSTRACT Lung development is a tightly regulated process that progresses through five distinct stages: embryonic, pseudoglandular, canalicular, saccular, and alveolar. Each stage is characterized by coordinated cellular interactions and structural changes driven by signals from epithelial, endothelial, and mesenchymal cells. The extracellular matrix (ECM) plays a pivotal role in this process, acting as both a structural scaffold and a dynamic regulator of cell behavior. Key ECM components, including collagens, elastin, proteoglycans, and glycosaminoglycans, provide the framework for tissue integrity while modulating critical signaling pathways essential for lung branching morphogenesis, alveolar formation, and vascular development. Disruptions in ECM dynamics are associated with pathological conditions such as bronchopulmonary dysplasia, chronic obstructive pulmonary disease, and pulmonary fibrosis. In these diseases, aberrant ECM remodeling leads to tissue stiffening, scarring, and impaired lung function. The ECM plays a critical role in storing and regulating the activity of growth factors, such as FGFs and VEGFs, thereby shaping cellular proliferation, differentiation, and repair processes. Understanding the complex interplay between ECM components and cellular signaling during normal and aberrant lung development provides valuable insights into therapeutic strategies aimed at restoring lung function. This review explores the multifaceted roles of proteoglycans and hyaluronan in lung development and disease, emphasizing its impact on tissue architecture, signaling environments, and repair processes.