Metformin is a novel suppressor for transforming growth factor (TGF)-β1
| Autor: | Jianli Liu, Zhizhen Lu, Han Xiao, Zhonghe Xu, Mingliang Zhang, Youyi Zhang, Jianshu Zhang, Yenan Feng, Xiaohong Fang, Jing Shen, Jimin Wu, Jingyuan Li, Ruifei Chen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty endocrine system diseases Biology Article 3T3 cells law.invention Transforming Growth Factor beta1 Mice 03 medical and health sciences 0302 clinical medicine Protein Domains law Diabetes mellitus Internal medicine medicine Animals Humans Receptor Multidisciplinary nutritional and metabolic diseases 3T3 Cells Surface Plasmon Resonance medicine.disease Polycystic ovary Metformin Molecular Docking Simulation 030104 developmental biology medicine.anatomical_structure Endocrinology 030220 oncology & carcinogenesis Cancer research Suppressor Signal transduction medicine.drug Transforming growth factor |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep28597 |
| Popis: | 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-β1 (TGF-β1), 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-β1 and found that metformin inhibits [125I]-TGF-β1 binding to its receptor. Furthermore, based on molecular docking and molecular dynamics simulations, metformin was predicted to interact with TGF-β1 at its receptor-binding domain. Single-molecule force spectroscopy revealed that metformin reduces the binding probability but not the binding force of TGF-β1 to its type II receptor. Consequently, metformin suppresses type II TGF-β1 receptor dimerization upon exposure to TGF-β1, which is essential for downstream signal transduction. Thus, our results indicate that metformin is a novel TGF-β suppressor with therapeutic potential for numerous diseases in which TGF-β1 hyperfunction is indicated. |
| Databáze: | OpenAIRE |
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