PDF(Pubmed)
Abstract：
Skeletal muscle atrophy is a morbidity and mortality risk factor that happens with disuse, chronic disease, and aging. The tissue remodeling that happens during recovery from atrophy or injury involves changes in different cell types such as muscle fibers, and satellite and immune cells. Here, we show that the previously uncharacterized gene and protein Zfp697 is a damage-induced regulator of muscle remodeling. Zfp697/ZNF697 expression is transiently elevated during recovery from muscle atrophy or injury in mice and humans. Sustained Zfp697 expression in mouse muscle leads to a gene expression signature of chemokine secretion, immune cell recruitment, and extracellular matrix remodeling. Notably, although Zfp697 is expressed in several cell types in skeletal muscle, myofiber-specific Zfp697 genetic ablation in mice is sufficient to hinder the inflammatory and regenerative response to muscle injury, compromising functional recovery. We show that Zfp697 is an essential mediator of the interferon gamma response in muscle cells and that it functions primarily as an RNA-interacting protein, with a very high number of miRNA targets. This work identifies Zfp697 as an integrator of cell-cell communication necessary for tissue remodeling and regeneration.
摘要：
骨骼肌萎缩是一种发病和死亡的危险因素，慢性疾病,和衰老。从萎缩或损伤恢复过程中发生的组织重塑涉及不同细胞类型的变化，如肌纤维，卫星和免疫细胞。这里,我们表明，以前未表征的基因和蛋白Zfp697是肌肉重塑的损伤诱导调节因子。Zfp697/ZNF697表达在小鼠和人的肌肉萎缩或损伤恢复期间短暂升高。小鼠肌肉中持续的Zfp697表达导致趋化因子分泌的基因表达特征，免疫细胞募集，和细胞外基质重塑。值得注意的是,虽然Zfp697在骨骼肌的几种细胞类型中表达，小鼠的肌纤维特异性Zfp697基因消融足以阻止对肌肉损伤的炎症和再生反应，影响功能恢复。我们证明Zfp697是肌细胞中干扰素γ反应的重要介质，它主要作为RNA相互作用蛋白起作用。具有非常高数量的miRNA靶标。这项工作将Zfp697确定为组织重塑和再生所必需的细胞间通讯的整合者。
