Zfp697 is an RNA- binding protein that regulates skeletal muscle inflammation and remodeling

• 成果类型: Article
• 署名作者: Correia, Jorge C.; Jannig, Paulo R.; Gosztyla, Maya L.; Cervenka, Igor; Ducommun, Serge; Praestholm, Stine M.; Dias, Jose M.; Dumont, Kyle D.; Liu, Zhengye; Liang, Qishan; Edsgaerd, Daniel; Emanuelsson, Olof; Gregorevic, Paul; Westerblad, Hakan; Venckunas, Tomas; Brazaitis, Marius; Kamandulis, Sigitas; Lanner, Johanna T.; Teixeira, Ana I.; Yeo, Gene W.; Ruas, Jorge L.
• 署名单位: Karolinska Institutet; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; Karolinska Institutet; Karolinska Institutet; Karolinska Institutet; University of California System; University of California San Diego; Royal Institute of Technology; University of Melbourne; Karolinska Institutet; Lithuanian Sports University; University of Michigan System; University of Michigan; University of Michigan System; University of Michigan
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11592
• DOI: 10.1073/pnas.2319724121
• 发表日期: 2024-08-20
• 关键词: duchenne muscular-dystrophy; regeneration; injury; cells; progression; mechanisms; deletion; GROWTH; ccl2

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 extra- cellular 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.