IMR Press / FBL / Volume 7 / Issue 4 / DOI: 10.2741/pinzani

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

PDGF and signal transduction in hepatic stellate cells
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1 Dipartimento di Medicina Interna, Università degli Studi di Firenze, Firenze, Italy
Academic Editors:Jian Wu, Pamela Norton
Front. Biosci. (Landmark Ed) 2002, 7(4), 1720–1726;
Published: 1 August 2002
(This article belongs to the Special Issue Liver fibrosis and targeting therapy)

Platelet-derived growth factor (PDGF) is one of the most potent mitogen for cultured HSC isolated from rat, mouse, or human liver. Phosphotyrosines on the activated PDGF receptor operate as high affinity binding sites for several molecules involved in the downstream propagation of the signal, including the sequential activation of Raf-1, MEK and extracellular-signal regulated kinase (ERK). Nuclear translocation of ERK is associated to the phosphorylation of several transcription factors, including Elk-1 and SAP, and represents an absolute requirement for triggering a proliferative response. Phosphatidylinositol 3-kinase (PI 3-K), is another molecule recruited by the activated PDGF receptor. In human HSC cultures, PI 3-K activation is necessary for both mitogenesis and chemotaxis induced by PDGF. In addition, PI 3-K is involved in the activation of the Ras-ERK pathway in human HSC, although it is not strictly necessary, since established PI 3-K inhibitors inhibit ERK activation only by 40-50%. Therefore, in HSC, PI 3-K regulates PDGF-related mitogenesis and cell migration by pathways that are at least in part independent of ERK activation. Accumulated evidence indicates that the induction of replicative competence by PDGF is dependent on the maintenance of sustained increase in [Ca2+]i due to calcium entry rather than from the release from intracellular stores. In addition, stimulation with PDGF increases the activity of the Na+/H+ exchanger in rat or human HSC with consequent sustained changes in intracellular pH.

Extracellular-regulated kinase
Focal adhesion kinase
Hepatic stellate cells
Platelet-derived growth factor
Signal transduction
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