國家衛生研究院 NHRI:Item 3990099045/13100
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    题名: Decorin inhibits the insulin-like growth factor I signaling in bone marrow mesenchymal stem cells of aged humans
    作者: Wong, TH;Chen, TY;Tseng, KY;Chen, ZY;Chen, CH;Lin, FH;Wu, HM;Lin, S
    贡献者: Institute of Biomedical Engineering and Nanomedicine;Institute of Population Health Sciences;National Institute of Infectious Diseases and Vaccinology
    摘要: Aging impairs the IGF-I signaling of bone marrow mesenchymal stem cells (bmMSCs), but the mechanism is unclear. Here, we found that the ability to auto-phosphorylate IGF-I receptor (IGF-IR) in response to IGF-I was decreased in the bmMSCs of aged donors. Conversely, data showed that decorin (DCN) expression was prominently increased in aged bmMSCs, and that under IGF-I treatment, DCN knockdown in serum-starved aged bmMSCs potentiated their mitogenic activity and IGF-IR auto-phosphorylation, whereas DCN overexpression in serum-starved adult bmMSCs decreased both activities. Co-immunoprecipitation assays suggested that IGF-I and DCN bound to IGF-IR in a competitive manner. Online MethPrimer predicted 4 CpG islands (CGIs) in the introns of DCN gene. RT-qPCR and bisulfite sequencing showed that dimethyloxalylglycine, an inhibitor of DNA demethylation, increased DCN mRNA expression and CGI-I methylation in adult bmMSCs, whereas 5-aza-2'-deoxycytidine, a DNA methylation inhibitor, decreased DCN mRNA expression and CGI-I methylation in aged bmMSCs, and ultimately enhanced the proliferation of serum-starved aged bmMSCs under IGF-I stimulation. Thus, IGF-IR could be the prime target of aging in down-regulating the IGF-I signaling of bmMSCs, where DCN could be a critical mediator.
    日期: 2021-01
    關聯: Aging. 2021 Jan;13(1):578-597.
    Link to: http://dx.doi.org/10.18632/aging.202166
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1945-4589&DestApp=IC2JCR
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85099562286
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