气候变化领域集成服务门户(CCPortal): FGF-2–dependent signaling activated in aged human skeletal muscle promotes intramuscular adipogenesis

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DOI	10.1073/pnas.2021013118
	FGF-2–dependent signaling activated in aged human skeletal muscle promotes intramuscular adipogenesis
	Mathes S.; Fahrner A.; Ghoshdastider U.; Rüdiger H.A.; Leunig M.; Wolfrum C.; Krützfeldt J.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:37
英文摘要	Aged skeletal muscle is markedly affected by fatty muscle infiltration, and strategies to reduce the occurrence of intramuscular adipocytes are urgently needed. Here, we show that fibroblast growth factor-2 (FGF-2) not only stimulates muscle growth but also promotes intramuscular adipogenesis. Using multiple screening assays upstream and downstream of microRNA (miR)-29a signaling, we located the secreted protein and adipogenic inhibitor SPARC to an FGF-2 signaling pathway that is conserved between skeletal muscle cells from mice and humans and that is activated in skeletal muscle of aged mice and humans. FGF-2 induces the miR-29a/SPARC axis through transcriptional activation of FRA-1, which binds and activates an evolutionary conserved AP-1 site element proximal in the miR-29a promoter. Genetic deletions in muscle cells and adeno-associated virus–mediated overexpression of FGF-2 or SPARC in mouse skeletal muscle revealed that this axis regulates differentiation of fibro/adipogenic progenitors in vitro and intramuscular adipose tissue (IMAT) formation in vivo. Skeletal muscle from human donors aged >75 y versus <55 y showed activation of FGF-2–dependent signaling and increased IMAT. Thus, our data highlights a disparate role of FGF-2 in adult skeletal muscle and reveals a pathway to combat fat accumulation in aged human skeletal muscle. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	FGF-2; FRA-1; IMAT; Skeletal muscle; SPARC
语种	英语
scopus关键词	complementary DNA; fatty acid binding protein 4; fibroblast growth factor 2; microRNA 29a; mitogen activated protein kinase kinase 1; mitogen activated protein kinase kinase 2; osteonectin; protein c jun; protein fos; protein p42; protein p44; small interfering RNA; transcription factor AP 1; transcription factor Fra 1; 3' untranslated region; 3T3 cell line; adipogenesis; adult; aged; animal cell; Article; cell differentiation; cell infiltration; controlled study; cytokine release; DNA synthesis; down regulation; human; human cell; in vitro study; in vivo study; lipid storage; mouse; muscle cell; muscle development; muscle growth; muscle regeneration; myoblast; nonhuman; Pi3K/Akt signaling; promoter region; protein expression; protein function; protein localization; protein phosphorylation; protein RNA binding; protein secretion; RNA extraction; signal transduction; skeletal muscle; transcription initiation; transcription initiation site; upregulation
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238805
作者单位	Division of Endocrinology, Diabetes, and Clinical Nutrition, University Hospital Zurich, Zurich, 8091, Switzerland; Biomedicine, Life Science Zurich Graduate School, University of Zurich, Zurich, 8057, Switzerland; Institute of Food, Nutrition and Health, Department of Health Sciences and Technology, Eidgenössische Technische Hochschule Zurich, Zurich, 8092, Switzerland; Department of Orthopaedics, Schulthess Clinic, Zurich, 8008, Switzerland
推荐引用方式 GB/T 7714	Mathes S.,Fahrner A.,Ghoshdastider U.,等. FGF-2–dependent signaling activated in aged human skeletal muscle promotes intramuscular adipogenesis[J],2021,118(37).
APA	Mathes S..,Fahrner A..,Ghoshdastider U..,Rüdiger H.A..,Leunig M..,...&Krützfeldt J..(2021).FGF-2–dependent signaling activated in aged human skeletal muscle promotes intramuscular adipogenesis.Proceedings of the National Academy of Sciences of the United States of America,118(37).
MLA	Mathes S.,et al."FGF-2–dependent signaling activated in aged human skeletal muscle promotes intramuscular adipogenesis".Proceedings of the National Academy of Sciences of the United States of America 118.37(2021).