Liu Yaoxia, Fan Zhen, Zhai Yang, Huang Haotian, Shi Ruifeng, Wang Tao
Department of Geriatric Endocrinology, Sichuan Provincial People's Hospital, School of medicine, University of Electronic Science and Technology of China, Chengdu, China.
Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
Front Cell Dev Biol. 2025 Jun 26;13:1594423. doi: 10.3389/fcell.2025.1594423. eCollection 2025.
Muscle development and metabolic homeostasis are critical aspects of human health. As a key component of the SWI/SNF chromatin remodeling complex, the BAF60 subunit plays a widespread and crucial role in the differentiation, reprogramming, and metabolic regulation of skeletal, cardiac, and smooth muscle. Recent studies reveal that BAF60c promotes skeletal muscle differentiation and regeneration by interacting with MyoD, while also driving cardiac-specific gene expression and cooperating with transcription factors such as NKX2.5 and GATA Binding Protein 4 (GATA4) during heart development and remodeling. In smooth muscle, BAF60c interacts with serum response factor to maintain contractility and homeostasis by reducing inflammation and apoptosis. In contrast, BAF60a promotes inflammatory responses and extracellular matrix degradation, contributing to vascular diseases such as abdominal aortic aneurysm and atherosclerosis. Importantly, different BAF60 isoforms exhibit antagonistic, synergistic, or mutually exclusive effects in different muscle types, highlighting their complexity. This review provides a comprehensive overview of BAF60 isoforms' regulatory roles, with an emphasis on their potential as therapeutic targets for muscle-related metabolic and vascular diseases.
肌肉发育和代谢稳态是人类健康的关键方面。作为SWI/SNF染色质重塑复合体的关键组成部分，BAF60亚基在骨骼肌、心肌和平滑肌的分化、重编程及代谢调节中发挥着广泛且关键的作用。最近的研究表明，BAF60c通过与MyoD相互作用促进骨骼肌分化和再生，同时在心脏发育和重塑过程中驱动心脏特异性基因表达，并与转录因子如NKX2.5和GATA结合蛋白4（GATA4）协同作用。在平滑肌中，BAF60c与血清反应因子相互作用，通过减少炎症和细胞凋亡来维持收缩性和稳态。相比之下，BAF60a促进炎症反应和细胞外基质降解，导致诸如腹主动脉瘤和动脉粥样硬化等血管疾病。重要的是，不同的BAF60亚型在不同肌肉类型中表现出拮抗、协同或互斥效应，凸显了它们的复杂性。本综述全面概述了BAF60亚型的调节作用，重点强调了它们作为肌肉相关代谢和血管疾病治疗靶点的潜力。
