{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nACTA2 encodes α‐smooth muscle actin, a critical contractile protein that underpins the function of vascular smooth muscle cells. By interacting cyclically with myosin, the ACTA2 gene product is essential for effective vessel contraction and blood flow regulation. Mutations in ACTA2 disrupt actin filament assembly and stability, resulting in diminished contractile force and predisposing affected individuals to a spectrum of vascular disorders—including thoracic aortic aneurysms and dissections, cerebrovascular abnormalities, and multisystem smooth muscle dysfunction syndromes. These pathogenic variants, whether inherited or de novo, underscore the indispensable role of ACTA2 in maintaining vascular structural integrity and function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its vascular role, ACTA2 is tightly regulated by mechanical forces and diverse biochemical signals that modulate myofibroblast differentiation and fibrotic remodeling in multiple tissues. Signaling cascades mediated by cytokines (e.g. TGF‐β and TNF‐α), microRNAs, and transcription factors (such as WT1) dynamically adjust ACTA2 expression during cellular responses to injury and changes in extracellular matrix stiffness. These processes underlie the formation of actin stress fibers in fibroblasts and myofibroblasts, thereby influencing tissue repair, wound contraction, and pathological fibrosis in organs like the lung, cornea, and kidney."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "18", "end_ref": "33"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence further expands the significance of ACTA2 beyond vascular biology into the realms of cancer biology and cellular differentiation. The α‐smooth muscle actin it encodes is frequently exploited as a biomarker to identify activated cancer‐associated fibroblasts, thereby serving as an indicator of stromal remodeling in various tumors. Moreover, ACTA2 expression marks progenitor cell differentiation and participates in the regenerative and neoplastic processes observed in settings such as basal cell carcinoma, pancreatic and esophageal cancers, and even in neural and hepatic fibrotic responses. Collectively, these diverse roles highlight the multifaceted influence of ACTA2 in both normal developmental processes and disease pathogenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "34", "end_ref": "47"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Dong-Chuan Guo, Hariyadarshi Pannu, Van Tran-Fadulu, et al. 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