2. Academic Validation
  3. Flavanomarein inhibits high glucose-stimulated epithelial-mesenchymal transition in HK-2 cells via targeting spleen tyrosine kinase

Flavanomarein inhibits high glucose-stimulated epithelial-mesenchymal transition in HK-2 cells via targeting spleen tyrosine kinase

  • Sci Rep. 2020 Jan 16;10(1):439. doi: 10.1038/s41598-019-57360-4.
Nan-Nan Zhang 1 2,  Jin-Sen Kang 2,  Shuai-Shuai Liu 3,  Si-Meng Gu 3,  Zhi-Peng Song 1 2,  Feng-Xiang Li 2,  Li-Feng Wang 4,  Lan Yao 5,  Tian Li 6,  Lin-Lin Li 2,  Ye Wang 2,  Xue-Jun Li  # 7,  Xin-Min Mao  # 8 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, Xinjiang Medical University, Urumqi, Xinjiang, 830011, China.
  • 2 Department of Pharmacology, Pharmacy College, Xinjiang Medical University, Urumqi, Xinjiang, 830011, China.
  • 3 Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
  • 4 Department of Physiology, Preclinical School, Xinjiang Medical University, Urumqi, Xinjiang, 830011, China.
  • 5 College of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi, Xinjiang, 830011, China.
  • 6 Department of Histology and Embryology, Preclinical College, XinJiang Medical University, Urumqi, Xinjiang, 830011, China.
  • 7 Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China. [email protected].
  • 8 State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, Xinjiang Medical University, Urumqi, Xinjiang, 830011, China. [email protected].
  • 9 College of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi, Xinjiang, 830011, China. [email protected].
  • # Contributed equally.
PMID: 31949205 DOI: 10.1038/s41598-019-57360-4
Abstract

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.

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