School of Life Sciences, Arizona State University, 427 E Tyler Mall, Tempe, AZ 85287, USA.
Molecular and Cellular Biology Graduate Program, Arizona State University, Tempe, AZ 85287, USA.
Int J Mol Sci. 2024 May 4;25(9):5019. doi: 10.3390/ijms25095019.
Efficient repair of skeletal muscle relies upon the precise coordination of cells between the satellite cell niche and innate immune cells that are recruited to the site of injury. The expression of pro-inflammatory cytokines and chemokines such as TNFα, IFNγ, CXCL1, and CCL2, by muscle and tissue resident immune cells recruits neutrophils and M1 macrophages to the injury and activates satellite cells. These signal cascades lead to highly integrated temporal and spatial control of muscle repair. Despite the therapeutic potential of these factors for improving tissue regeneration after traumatic and chronic injuries, their transcriptional regulation is not well understood. The transcription factor Mohawk () functions as a repressor of myogenic differentiation and regulates fiber type specification. Embryonically, is expressed in all progenitor cells of the musculoskeletal system and is expressed in human and mouse myeloid lineage cells. An analysis of mice deficient for revealed a delay in postnatal muscle repair characterized by impaired clearance of necrotic fibers and smaller newly regenerated fibers. Further, there was a delay in the expression of inflammatory signals such as , , and This was coupled with impaired recruitment of pro-inflammatory macrophages to the site of muscle damage. These studies demonstrate that plays a critical role in adult skeletal muscle repair that is mediated through the initial activation of the inflammatory response.
骨骼肌的有效修复依赖于卫星细胞龛和固有免疫细胞之间的精确细胞协调，这些细胞被募集到损伤部位。肌肉和组织驻留免疫细胞表达的促炎细胞因子和趋化因子，如 TNFα、IFNγ、CXCL1 和 CCL2，招募中性粒细胞和 M1 巨噬细胞到损伤部位，并激活卫星细胞。这些信号级联反应导致肌肉修复的高度集成的时空控制。尽管这些因子在创伤和慢性损伤后改善组织再生方面具有治疗潜力，但它们的转录调控尚不清楚。转录因子 Mohawk () 作为肌生成分化的抑制剂，调节纤维类型特异性。在胚胎期， 在骨骼肌肉系统的所有祖细胞中表达，并在人和鼠髓系细胞中表达。对缺乏 的小鼠进行分析表明，肌肉修复延迟，其特征为坏死纤维清除受损和新再生纤维更小。此外，炎症信号如 、 和 的表达也出现延迟。这伴随着促炎巨噬细胞向肌肉损伤部位募集的受损。这些研究表明， 在成年骨骼肌修复中发挥关键作用，其通过炎症反应的初始激活来介导。
