Cross-talk between PDGF and S1P signalling elucidates the inhibitory effect and potential antifibrotic action of the immunomodulator FTY720 in activated HSC-cultures. (Articolo in rivista)

Type
Label
  • Cross-talk between PDGF and S1P signalling elucidates the inhibitory effect and potential antifibrotic action of the immunomodulator FTY720 in activated HSC-cultures. (Articolo in rivista) (literal)
Anno
  • 2008-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1016/j.bbamcr.2007.11.008, (literal)
Alternative label
  • Anna Maria Brunati a; Elena Tibaldi; Amedeo Carraro, Enrico Gringeri; Francesco D'Amico Jr; Antonio Toninello; Maria Lina Massimino; Mario Angelo Pagano; Giovanna Nalesso; Umberto Cillo. (2008)
    Cross-talk between PDGF and S1P signalling elucidates the inhibitory effect and potential antifibrotic action of the immunomodulator FTY720 in activated HSC-cultures.
    in Biochimica et biophysica acta. Molecular cell research
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Anna Maria Brunati a; Elena Tibaldi; Amedeo Carraro, Enrico Gringeri; Francesco D'Amico Jr; Antonio Toninello; Maria Lina Massimino; Mario Angelo Pagano; Giovanna Nalesso; Umberto Cillo. (literal)
Pagina inizio
  • 347 (literal)
Pagina fine
  • 359 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 1783 (literal)
Rivista
Note
  • Scopus (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • Department of Biochemistry, University of Padova, Viale G. Colombo 3, 35121, Padova, Italy Department of General Surgery and Organ Transplantation, Hepatobiliary and Liver Transplant Unit, University of Padova, Via Giustiniani 2, 35128, Padova, Italy Chirurgia Oncologica, IOV- Istituto Oncologico Veneto, IRCCS, Via Gattamelata 64, 35128, Padova, Italy d CNR Institute of Neuroscience, viale G. Colombo 3, 35121 Padova, Italy (literal)
Titolo
  • Cross-talk between PDGF and S1P signalling elucidates the inhibitory effect and potential antifibrotic action of the immunomodulator FTY720 in activated HSC-cultures. (literal)
Abstract
  • Platelet-derived growth factor (PDGF) has been shown to be essential in the activation of hepatic stellate cells (HSCs), contributing to the onset and development of hepatic fibrosis. Recently, sphingosine-1-phosphate (S1P) has been shown to be a mitogen and stimulator of chemotaxis also for HSCs. Since it has been demonstrated in several cell types that cross-talk between PDGF and S1P signalling pathways occurs, our aim was to investigate the potential antifibrotic effect of FTY720, whose phosphorylated form acts as a potent S1P receptor (S1PR) modulator, on HSCs. FTY720 inhibits cell proliferation and migration after PDGF stimulation on HSCs in a concentration range between 0.1 and 1 ?M. By using compounds that block S1P signalling (PTX and VPC23019), we assessed that FTY720 also acts in an S1P receptor-independent way by decreasing the level of tyrosine phosphorylation of PDGF receptor, with subsequent inhibition of the PDGF signalling pathway. In addition, inhibition of sphingosine kinase2 (SphK2), which is responsible for FTY720 phosphorylation, by DMS/siRNA unveils a mechanism of action irrespective of its phosphorylation, in particular decreasing the level of S1P1 on the plasma membrane. These findings led us to hypothesize a potential use of FTY720 as a potential antifibrotic drug for further clinical application. (literal)
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