Lung Pericytes: Molecular Mechanisms, Signaling Pathways, and Roles in Pulmonary Diseases

Pericytes are specialized mural cells that ensheathe microvessels and play critical roles in maintaining vascular homeostasis, regulating angiogenesis, and coordinating tissue repair. Studies in the systemic circulation have established that pericytes contribute to the pathogenesis of major vascular diseases, including stroke, myocardial infarction, and retinopathy, increasing interest in understanding their roles in both health and disease. In contrast, our understanding of pericyte biology in the lung remains relatively limited. Over the past 15 years, a growing body of evidence emphasizes that lung pericytes actively participate in vascular remodeling and inflammatory responses, pointing to an important role for these cells in the pathogenesis of multiple pulmonary diseases. This comprehensive review synthesizes current knowledge on the molecular mechanisms governing lung pericyte function, with particular emphasis on key signaling pathways including PDGF-BB/PDGFRβ, TGFβ/ALK1/ALK5, VEGF/VEGFR, Angiopoietin/Tie2, Notch, Wnt, and sphingosine-1-phosphate (S1P). We examine how these pathways orchestrate pericyte recruitment, proliferation, differentiation, and phenotypic transitions through complex downstream signaling cascades involving kinases, transcription factors, and mechanotransduction mechanisms. The review further explores the multifaceted roles of pericytes in major pulmonary diseases, including acute lung injury and acute respiratory distress syndrome (ALI/ARDS), pulmonary fibrosis, pulmonary arterial hypertension (PAH), lung cancer, and lung infections.