https://scholars.lib.ntu.edu.tw/handle/123456789/577138
標題: | Decorin inhibits the insulin-like growth factor I signaling in bone marrow mesenchymal stem cells of aged humans | 作者: | Wong T.-H Chen T.-Y Tseng K.-Y Chen Z.-Y Chen C.-H Lin F.-H Wu H.-M Lin S. Lin, Feng-Huei |
關鍵字: | DCN protein, human; decitabine; decorin; dicarboxylic amino acid; enzyme inhibitor; IGF1 protein, human; messenger RNA; oxalylglycine; somatomedin C; somatomedin C receptor; adult; aged; aging; bone marrow cell; DNA demethylation; DNA methylation; drug effect; gene expression regulation; gene knockdown; genetics; human; mesenchymal stem cell; metabolism; middle aged; phosphorylation; signal transduction; Adult; Aged; Aging; Amino Acids, Dicarboxylic; Bone Marrow Cells; Decitabine; Decorin; DNA Demethylation; DNA Methylation; Enzyme Inhibitors; Gene Expression Regulation, Developmental; Gene Knockdown Techniques; Humans; Insulin-Like Growth Factor I; Mesenchymal Stem Cells; Middle Aged; Phosphorylation; Receptor, IGF Type 1; RNA, Messenger; Signal Transduction | 公開日期: | 2021 | 卷: | 13 | 期: | 1 | 起(迄)頁: | 578-597 | 來源出版物: | Aging | 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. ? 2020. Wong et al. All Rights Reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85099562286&doi=10.18632%2faging.202166&partnerID=40&md5=c03455b2d37978dac6b5158bb6d02fd4 https://scholars.lib.ntu.edu.tw/handle/123456789/577138 |
ISSN: | 19454589 | DOI: | 10.18632/aging.202166 |
顯示於: | 醫學工程學研究所 |
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