The emerging role of integrin signaling in pulmonary vascular disease

Integrin signaling promotes cellular proliferation, inflammation, and fibrosis in various forms of lung diseases, including pulmonary fibrosis, asthma, and acute respiratory distress syndrome. Recent studies suggest the promising role of integrins in the pathogenesis of pulmonary arterial hypertension, a morbid and incurable disease. In this review, we explore the biologic basis of integrins in potentiating pulmonary vascular disease and their candidacy as treatment targets. Specifically, we explore integrin-derived effects implicated in the pathobiology of pulmonary vascular disease, such as TGF-β activation, neointima formation, and inflammatory cell recruitment. We discuss intracellular pathways involving cytoplasmic kinases and matrisomal integrin ligands that are studied in the specific context of pulmonary vascular disease, focusing on recent therapeutic animal studies targeting integrin biology. Finally, we summarize unanswered knowledge gaps in the pursuit of therapeutic translation of integrin modulation.