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TSG attenuates LPC ‐induced endothelial cells inflammatory damage through notch signaling inhibition
Author(s) -
Zhao Jing,
Liang Yuan,
Song Fan,
Xu Shouzhu,
Nian Lun,
Zhou Xuanxuan,
Wang Siwang
Publication year - 2016
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.1458
Subject(s) - notch signaling pathway , hes1 , microbiology and biotechnology , lysophosphatidylcholine , hes3 signaling axis , signal transduction , inflammation , endothelial stem cell , chemistry , cancer research , biology , immunology , biochemistry , phospholipid , membrane , phosphatidylcholine , in vitro
Abstract Lysophosphatidylcholine (LPC) induces inflammation in endothelial cells (ECs) but the mechanism is not fully understood. The Notch signaling pathway is involved in chronic EC inflammation, but its functions in LPC‐induced endothelial inflammatory damage and 2,3,5,4′‐tetrahydroxystilbene‐2‐ O ‐β‐ d ‐glucoside's (TSG) protective effect during LPC‐induced inflammatory damage in human umbilical vein endothelial cells (HUVECs) is largely unknown. We report that Notch signaling activation contributed to LPC‐induced injury in HUVECs, and that TSG protected HUVECs from LPC‐induced injury by antagonizing Notch signaling activation by LPC. γ‐secretase inhibitor (DAPT), a specific inhibitor of the Notch signaling pathway, and Notch1 siRNA were used to inhibit Notch activity. HUVECs were exposed to LPC in the presence or absence of TSG, DAPT, and Notch1 siRNA. LPC treatment of HUVECs resulted in reduced cell viability, and Notch1 and Hes1 upregulation. Either silencing of Notch1 by siRNA or pharmacological inhibition of Notch signaling by DAPT prevented the loss of cell viability, and induction of apoptosis, and enhanced expression Notch1, Hes1 and MCP‐1 by LPC in HUVECs. Similarly, TSG reduced LPC stimulation of Notch1, Hes1, and MCP‐1 expression, prevented the release of IL‐6 and CRP and rescued HUVECs from LPC‐induced cell damage. Our data indicate that the Notch signaling pathway is a crucial mediator of endothelial inflammatory damage and that TSG protects against endothelial inflammatory damage by inhibiting the Notch signaling pathway. Our findings suggest that targeting Notch signaling by natural products such as TSG is a promising strategy for the prevention and treatment of chronic inflammation associated diseases, including atherosclerosis. © 2015 IUBMB Life, 68(1):37–50, 2016