PDF(Pubmed)
Abstract：
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 (Mkx) functions as a repressor of myogenic differentiation and regulates fiber type specification. Embryonically, Mkx 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 Mkx 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 Ccl2, Ifnγ, and Tgfß. This was coupled with impaired recruitment of pro-inflammatory macrophages to the site of muscle damage. These studies demonstrate that Mkx plays a critical role in adult skeletal muscle repair that is mediated through the initial activation of the inflammatory response.
摘要：
骨骼肌的有效修复依赖于卫星细胞小生境和被募集到损伤部位的先天免疫细胞之间的细胞的精确协调。促炎细胞因子和趋化因子如TNFα的表达，IFNγ,CXCL1和CCL2通过肌肉和组织驻留的免疫细胞募集嗜中性粒细胞和M1巨噬细胞来损伤并激活卫星细胞。这些信号级联导致肌肉修复的高度整合的时间和空间控制。尽管这些因素对改善创伤和慢性损伤后组织再生具有治疗潜力，它们的转录调控还没有得到很好的理解。转录因子Mohawk（Mkx）充当肌源性分化的阻遏物，并调节纤维类型的规格。胚胎，Mkx在肌肉骨骼系统的所有祖细胞中表达,并在人和小鼠髓系细胞中表达。对缺乏Mkx的小鼠的分析表明，出生后的肌肉修复延迟，其特征是坏死纤维和较小的新再生纤维的清除受损。Further,炎症信号如Ccl2、Ifnγ、和Tgfβ。这与促炎巨噬细胞向肌肉损伤部位的受损募集有关。这些研究表明，Mkx在成人骨骼肌修复中起关键作用，这是通过炎症反应的初始激活介导的。
