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

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-?1/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.

SUBMITTER: Zhang NN

PROVIDER: S-EPMC6965095 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Zhang Nan-Nan NN Kang Jin-Sen JS Liu Shuai-Shuai SS Gu Si-Meng SM Song Zhi-Peng ZP Li Feng-Xiang FX Wang Li-Feng LF Yao Lan L Li Tian T Li Lin-Lin LL Wang Ye Y Li Xue-Jun XJ Mao Xin-Min XM

Scientific reports 20200116 1

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 pr ...[more]

PMID: 31949205

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Dataset Information

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

Publications

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

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