title: TSG attenuates LPC-induced endothelial cells inflammatory damage through notch signaling inhibition.
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.
authors.affiliation: Department of Natural Medicine, School of Pharmacy, the Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pathology, the Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Natural Medicine, School of Pharmacy, the Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Fan
authors.initials: F
authors.lastname: Song
authors.affiliation: Department of Natural Medicine, School of Pharmacy, the Fourth Military Medical University, Xi'an, 710032, People's Republic of China.|Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an, People's Republic of China.
authors.forename: Shouzhu
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Natural Medicine, School of Pharmacy, the Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Lun
authors.initials: L
authors.lastname: Nian
authors.affiliation: Department of Natural Medicine, School of Pharmacy, the Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Xuanxuan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Natural Medicine, School of Pharmacy, the Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Siwang
authors.initials: S
authors.lastname: Wang
mesh_terms: D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D002470:Cell Survival; D018932:Chemokine CCL2 / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D005960:Glucosides / Q000494:pharmacology*; D018398:Homeodomain Proteins / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology*; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002097:C-Reactive Protein; D018932:Chemokine CCL2; D004151:Dipeptides; D005960:Glucosides; D018398:Homeodomain Proteins; D015850:Interleukin-6; D008244:Lysophosphatidylcholines; D051881:Receptor, Notch1; D013267:Stilbenes; D000072056:Transcription Factor HES-1; C111835:CCL2 protein, human; C508600:IL6 protein, human; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester; C497761:NOTCH1 protein, human; C093026:2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside; C078493:HES1 protein, human
keywords: LPC; Notch signaling pathway; TSG; inflammation