Flavanomarein inhibits high glucose-stimulated epithelial-mesenchymal transition in HK-2 cells via targeting spleen tyrosine kinase
| Autor: | Si-Meng Gu, Lifeng Wang, Lan Yao, Jin-sen Kang, Tian Li, Nan nan Zhang, Shuai-Shuai Liu, Zhi-peng Song, Ye Wang, Linlin Li, Xuejun Li, Xinmin Mao, Feng-xiang Li |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Epithelial-Mesenchymal Transition Protein Conformation lcsh:Medicine Syk Smad Proteins SMAD Kidney Biochemistry Article Cell Line Transforming Growth Factor beta1 03 medical and health sciences 0302 clinical medicine Protein structure Western blot Renal fibrosis Target identification medicine Humans Syk Kinase Vimentin Epithelial–mesenchymal transition lcsh:Science Cell Proliferation Multidisciplinary Dose-Response Relationship Drug medicine.diagnostic_test Chemistry lcsh:R Cadherins Actins Fibronectins Cell biology Molecular Docking Simulation Glucose 030104 developmental biology Gene Expression Regulation Cell culture 030220 oncology & carcinogenesis lcsh:Q Signal transduction Signal Transduction Transforming growth factor |
| Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020) Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-019-57360-4 |
| Popis: | Flavanomarein (FM) is a major natural compound of Coreopsis tinctoria Nutt with protective effects against diabetic nephropathy (DN). In this study, we investigated the effects of FM on epithelial-mesenchymal transition (EMT) in high glucose (HG)-stimulated human proximal tubular epithelial cells (HK-2) and the underlying mechanisms, including both direct targets and downstream signal-related proteins. The influence of FM on EMT marker proteins was evaluated via western blot. Potential target proteins of FM were searched using Discovery Studio 2017 R2. Gene Ontology (GO) analysis was conducted to enrich the proteins within the protein-protein interaction (PPI) network for biological processes. Specific binding of FM to target proteins was examined via molecular dynamics and surface plasmon resonance analyses (SPR). FM promoted the proliferation of HK-2 cells stimulated with HG and inhibited EMT through the Syk/TGF-β1/Smad signaling pathway. Spleen tyrosine kinase (Syk) was predicted to be the most likely directly interacting protein with FM. Combined therapy with a Syk inhibitor and FM presents significant potential as an effective novel therapeutic strategy for DN. |
| Databáze: | OpenAIRE |
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