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Metformin is a novel suppressor for transforming growth factor (TGF)-beta 1
Xiao, H; Zhang, JS; Xu ZH(徐钟河); Li JY(李敬源); Xu, ZH; Feng, YA; Zhang, ML; Liu, JL; Chen, RF; Shen, J; Wu, JM; Lu, ZZ; Fang, XH; Li, JY; Zhang, YY
2016
发表期刊SCIENTIFIC REPORTS
卷号6
文章类型期刊论文
摘要Metformin is a widely used first-line antidiabetic drug that has been shown to protect against a variety of specific diseases in addition to diabetes, including cardiovascular disorders, polycystic ovary syndrome, and cancer. However, the precise mechanisms underlying the diverse therapeutic effects of metformin remain elusive. Here, we report that transforming growth factor-beta 1 (TGF-beta 1), which is involved in the pathogenesis of numerous diseases, is a novel target of metformin. Using a surface plasmon resonance-based assay, we identified the direct binding of metformin to TGF-beta 1 and found that metformin inhibits [I-125]-TGF-beta 1 binding to its receptor. Furthermore, based on molecular docking and molecular dynamics simulations, metformin was predicted to interact with TGF-beta 1 at its receptor-binding domain. Single-molecule force spectroscopy revealed that metformin reduces the binding probability but not the binding force of TGF-beta 1 to its type II receptor. Consequently, metformin suppresses type II TGF-beta 1 receptor dimerization upon exposure to TGF-beta 1, which is essential for downstream signal transduction. Thus, our results indicate that metformin is a novel TGF-beta suppressor with therapeutic potential for numerous diseases in which TGF-beta 1 hyperfunction is indicated.
DOI10.1038/srep28597
关键词[WOS]BETA SIGNALING PATHWAY ; FORCE-FIELD ; CANCER ; FIBROSIS ; RECEPTOR ; THERAPY ; DISEASE ; CELLS
语种英语
WOS类目Multidisciplinary Sciences
WOS记录号WOS:000378789000001
引用统计
被引频次:13[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.ihep.ac.cn/handle/311005/260407
专题多学科研究中心
作者单位中国科学院高能物理研究所
推荐引用方式
GB/T 7714
Xiao, H,Zhang, JS,Xu ZH,et al. Metformin is a novel suppressor for transforming growth factor (TGF)-beta 1[J]. SCIENTIFIC REPORTS,2016,6.
APA Xiao, H.,Zhang, JS.,徐钟河.,李敬源.,Xu, ZH.,...&Zhang, YY.(2016).Metformin is a novel suppressor for transforming growth factor (TGF)-beta 1.SCIENTIFIC REPORTS,6.
MLA Xiao, H,et al."Metformin is a novel suppressor for transforming growth factor (TGF)-beta 1".SCIENTIFIC REPORTS 6(2016).
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