The Role of Aryl Hydrocarbon Receptor in Airway Remodeling: Mechanistic Insights Across Cellular Functions

Airway remodeling, a hallmark of asthma, involves structural and functional changes in the airways including extracellular matrix (ECM) deposition, airway smooth muscle (ASM) cell hypertrophy and hyperplasia, epithelial and fibroblasts remodeling, and mitochondrial dysfunction driven by chronic inflammation. The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor commonly known for mediating xenobiotic responses, has recently emerged as a key regulator of cellular processes implicated in airway remodeling. This review explores the multifaceted role of AhR in modulating proliferation, migration, ECM remodeling, contraction, and mitochondrial homeostasis across various airway structural cell types. Based on recent studies, we highlight how AhR exerts anti-proliferative effects in ASM, epithelial, and fibroblasts, modulates calcium signaling to influence contraction, and regulates ECM turnover via transforming growth factor-β and matrix metallopeptidase pathways. Additionally, the dual, ligand- and context-dependent nature of AhR activation is emphasized, with both protective and detrimental outcomes observed depending on the specific agonist and disease conditions. Collectively, this review underscores the therapeutic potential of targeting AhR in airway remodeling.