骨骼肌
生物
细胞生物学
心肌细胞
炎症
细胞外基质
再生(生物学)
肌肉萎缩
萎缩
免疫系统
基因表达
免疫学
内分泌学
基因
遗传学
作者
Jorge C. Correia,Paulo R. Jannig,Maya L. Gosztyla,Igor Červenka,Serge Ducommun,Stine M. Præstholm,José M. Dias,Kyle D. Dumont,Zhengye Liu,Qishan Liang,Daniel Edsgärd,Olof Emanuelsson,Paul Gregorevic,Håkan Westerblad,Tomas Venckūnas,Marius Brazaitis,Sigitas Kamandulis,Johanna T. Lanner,Ana I. Teixeira,G Yeo,Jorge L. Ruas
标识
DOI:10.1073/pnas.2319724121
摘要
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.
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