Bivalent ligand UDCA-LPE inhibits pro-fibrogenic integrin signalling by inducing lipid raft-mediated internalization

• Verfasst von: Su, Jie [VerfasserIn]
• Verfasst von: Gan-Schreier, Hongying [VerfasserIn]
• Verfasst von: Goeppert, Benjamin [VerfasserIn]
• Verfasst von: Chamulitrat, Walee [VerfasserIn]
• Verfasst von: Stremmel, Wolfgang [VerfasserIn]
• Verfasst von: Pathil-Warth, Anita [VerfasserIn]
• Titel: Bivalent ligand UDCA-LPE inhibits pro-fibrogenic integrin signalling by inducing lipid raft-mediated internalization
• Verf.angabe: Jie Su, Hongying Gan-Schreier, Benjamin Goeppert, Walee Chamulitrat, Wolfgang Stremmel and Anita Pathil
• E-Jahr: 2018
• Jahr: 20 October 2018
• Umfang: 15 S.
• Titel Quelle: Enthalten in: International journal of molecular sciences
• Ort Quelle: Basel : Molecular Diversity Preservation International, 2000
• Jahr Quelle: 2018
• Band/Heft Quelle: 19(2018), 10, Artikel-ID 3254, Seite 1-15
• ISSN Quelle: 1422-0067
• ISSN Quelle: 1661-6596
• DOI: doi:10.3390/ijms19103254
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: hepatic fibrosis
• Sach-SW: integrin signalling
• Sach-SW: lipid raft-mediated internalization
• K10plus-PPN: 1584190817
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

Ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE) is a synthetic bile acid-phospholipid conjugate with profound hepatoprotective and anti-fibrogenic functions in vitro and in vivo. Herein, we aimed to demonstrate the inhibitory effects of UDCA-LPE on pro-fibrogenic integrin signalling. UDCA-LPE treatment of human embryonic liver cell line CL48 and primary human hepatic stellate cells induced a non-classical internalization of integrin β1 resulting in dephosphorylation and inhibition of SRC and focal adhesion kinase (FAK). Signalling analyses suggested that UDCA-LPE may act as a heterobivalent ligand for integrins and lysophospholipid receptor1 (LPAR1) and co-immunoprecipitation demonstrated the bridging effect of UDCA-LPE on integrin β1 and LPAR1. The disruption of either the UDCA-moiety binding to integrins by RGD-containing peptide GRGDSP or the LPE-moiety binding to LPAR1 by LPAR1 antagonist Ki16425 reversed inhibitory functions of UDCA-LPE. The lack of inhibitory functions of UDCA-PE and UDCA-LPE derivatives (14:0 and 12:0, LPE-moiety containing shorter fatty acid chain) as well as the consistency of the translocation of UDCA-LPE and integrins, which co-fractionated with LPE but not UDCA, suggested that the observed UDCA-LPE-induced translocation of integrins was mediated by LPE endocytic transport pathway.