Rearrangement of the cytoskeletal network induced by platelet-derived growth factor in rat hepatic stellate cells: role of different intracellular signalling pathways.
OBJECTIVE
Cytoskeletal reorganization plays an important role in the regulation of different cell functions, such as proliferation and migration. Since platelet-derived growth factor (PDGF) stimulates both proliferation and chemotaxis of hepatic stellate cells (HSC), we investigated the effects of this cytokine on cytoskeletal components of cultured rat HSC.


RESULTS
Exposure of HSC to PDGF induced the formation of stress fibres and of a ruffled configuration of the plasma membrane, evaluated by both fluorescence and electron microscopy. These modifications were also induced by exposure to the protein kinase C (PKC) activator phorbol-12-myristate-13-acetate (PMA) and abolished by pretreatment with the PKC inhibitor calphostin C, with the Rho inhibitor C3 exoenzyme and with the intracellular calcium chelator MAPTAM, but not with the PI-3 kinase inhibitor wortmannin or with the mitogen-activated protein kinase kinase inhibitor PD 98059. PDGF induced a translocation of Rho from the cytosol to the membrane which was inhibited by C3 exoenzyme and by calpostin C, and which was also induced by PMA. Moreover, PDGF induced a rearrangement of vinculin which was prevented by C3 exoenzyme and calphostin C.


CONCLUSIONS
PDGF-induced cytoskeletal reorganization in HSC is dependent on PKC and Rho, thus suggesting that these two pathways may play an important role in the response of liver to injury.
Di Sario
Antonio
A
Department of Gastroenterology, University of Ancona, 60020 Torrette, Ancona, Italy. a.disario@popsci.unian.it
Bendia
Emanuele
E
Svegliati-Baroni
Gianluca
G
Marzioni
Marco
M
Ridolfi
Francesco
F
Trozzi
Luciano
L
Ugili
Laura
L
Saccomanno
Stefania
S
Jezequel
Anne Marie
AM
Benedetti
Antonio
A
D036002:ADP Ribose Transferases / Q000494:pharmacology; D000818:Animals; D001905:Botulinum Toxins; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D022502:Stress Fibers / Q000187:drug effects / Q000378:metabolism; D016596:Vinculin / Q000032:analysis; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D004791:Enzyme Inhibitors; D010982:Platelet-Derived Growth Factor; D016596:Vinculin; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D011493:Protein Kinase C; D001905:Botulinum Toxins; D020741:rho GTP-Binding Proteins