Yaoxia Liu, Zhen Fan, Yang Zhai, Haotian Huang, Ruifeng Shi, Tao Wang
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引用次数: 0
摘要
肌肉发育和代谢稳态是人类健康的重要方面。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、心脏和平滑肌的分化、重编程和代谢调节中发挥着广泛而关键的作用。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NKX2.5和GATA Binding Protein 4 (GATA4)等转录因子合作。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力和体内平衡。相反,BAF60a促进炎症反应和细胞外基质降解,促进血管疾病,如腹主动脉瘤和动脉粥样硬化。重要的是,不同的BAF60亚型在不同的肌肉类型中表现出拮抗、协同或互斥作用,突出了它们的复杂性。本文综述了BAF60亚型的调控作用,重点介绍了它们作为肌肉相关代谢和血管疾病的治疗靶点的潜力。
The multifaceted roles of BAF60 subunits in muscle: regulation of differentiation, reprogramming, and metabolic homeostasis.
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.
期刊介绍:
Frontiers in Cell and Developmental Biology is a broad-scope, interdisciplinary open-access journal, focusing on the fundamental processes of life, led by Prof Amanda Fisher and supported by a geographically diverse, high-quality editorial board.
The journal welcomes submissions on a wide spectrum of cell and developmental biology, covering intracellular and extracellular dynamics, with sections focusing on signaling, adhesion, migration, cell death and survival and membrane trafficking. Additionally, the journal offers sections dedicated to the cutting edge of fundamental and translational research in molecular medicine and stem cell biology.
With a collaborative, rigorous and transparent peer-review, the journal produces the highest scientific quality in both fundamental and applied research, and advanced article level metrics measure the real-time impact and influence of each publication.