The G protein-coupled bile acid receptor TGR5 (Gpbar1) modulates endothelin-1 signaling in liver

Simple item page
dc.contributor.authorKlindt, Caroline
dc.contributor.authorReich, Maria
dc.contributor.authorHellwig, Birte
dc.contributor.authorStindt, Jan
dc.contributor.authorRahnenführer, Jörg
dc.contributor.authorHengstler, Jan G.
dc.contributor.authorKöhrer, Karl
dc.contributor.authorSchoonjans, Kristina
dc.contributor.authorHäussinger, Dieter
dc.contributor.authorKeitel, Verena
dc.date.accessioned2020-01-29T09:37:59Z
dc.date.available2020-01-29T09:37:59Z
dc.date.issued2019-11-19
dc.description.abstractTGR5 (Gpbar1) is a G protein-coupled receptor responsive to bile acids (BAs), which is expressed in different non-parenchymal cells of the liver, including biliary epithelial cells, liver-resident macrophages, sinusoidal endothelial cells (LSECs), and activated hepatic stellate cells (HSCs). Mice with targeted deletion of TGR5 are more susceptible towards cholestatic liver injury induced by cholic acid-feeding and bile duct ligation, resulting in a reduced proliferative response and increased liver injury. Conjugated lithocholic acid (LCA) represents the most potent TGR5 BA ligand and LCA-feeding has been used as a model to rapidly induce severe cholestatic liver injury in mice. Thus, TGR5 knockout (KO) mice and wildtype (WT) littermates were fed a diet supplemented with 1% LCA for 84 h. Liver injury and gene expression changes induced by the LCA diet revealed an enrichment of pathways associated with inflammation, proliferation, and matrix remodeling. Knockout of TGR5 in mice caused upregulation of endothelin-1 (ET-1) expression in the livers. Analysis of TGR5-dependent ET-1 signaling in isolated LSECs and HSCs demonstrated that TGR5 activation reduces ET-1 expression and secretion from LSECs and triggers internalization of the ET-1 receptor in HSCs, dampening ET-1 responsiveness. Thus, we identified two independent mechanisms by which TGR5 inhibits ET-1 signaling and modulates portal pressure.en
dc.identifier.urihttp://hdl.handle.net/2003/38540
dc.identifier.urihttp://dx.doi.org/10.17877/DE290R-20459
dc.language.isoende
dc.relation.ispartofseriesCells;8(11)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectBile acidsen
dc.subjectEndothelin-1en
dc.subjectSinusoidal endothelial cellsen
dc.subjectHepatic stellate cellsen
dc.subjectPortal hypertensionen
dc.subject.ddc310
dc.titleThe G protein-coupled bile acid receptor TGR5 (Gpbar1) modulates endothelin-1 signaling in liveren
dc.typeTextde
dc.type.publicationtypearticlede
dcterms.accessRightsopen access
eldorado.secondarypublicationtruede
eldorado.secondarypublication.primarycitationKlindt, C.; Reich, M.; Hellwig, B.; Stindt, J.; Rahnenführer, J.; Hengstler, J.G.; Köhrer, K.; Schoonjans, K.; Häussinger, D.; Keitel, V. The G Protein-Coupled Bile Acid Receptor TGR5 (Gpbar1) Modulates Endothelin-1 Signaling in Liver. Cells 2019, 8, 1467.de
eldorado.secondarypublication.primaryidentifierhttps://doi.org/10.3390/cells8111467de

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
cells-08-01467.pdf
Size:
4.84 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
4.85 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Statistische Methoden in der Genetik und Chemometrie