http://www.cnr.it/ontology/cnr/individuo/prodotto/ID13962
TGF-beta1 targets the GSK-3beta/beta-catenin pathway via ERK activation in the transition of human lung fibroblasts into myofibroblasts (Articolo in rivista)
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- TGF-beta1 targets the GSK-3beta/beta-catenin pathway via ERK activation in the transition of human lung fibroblasts into myofibroblasts (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.phrs.2008.02.001 (literal)
- Alternative label
Caraci F, Gili E, Calafiore M, Failla M, La Rosa C, Crimi N, Sortino MA, Nicoletti F, Copani A, Vancheri C (2008)
TGF-beta1 targets the GSK-3beta/beta-catenin pathway via ERK activation in the transition of human lung fibroblasts into myofibroblasts
in Pharmacological research (Print)
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- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Caraci F, Gili E, Calafiore M, Failla M, La Rosa C, Crimi N, Sortino MA, Nicoletti F, Copani A, Vancheri C (literal)
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- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
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- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo
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- ISI Web of Science (WOS) (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
- a Department of Pharmaceutical Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy
b Department of Internal and Specialistic Medicine, Section of Respiratory Medicine, University of Catania,
Via Passo Gravina 187, 95125 Catania, Italy
c Department of Experimental and Clinical Pharmacology, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy
d Department of Human Physiology and Pharmacology, University of Rome La Sapienza,
Piazzale Aldo Moro 5, 00185 Rome, Italy
e I.N.M. Neuromed, Localit`a Camerelle, 86077 Pozzilli, Italy
f I.B.B., CNR-Catania, Italy (literal)
- Titolo
- TGF-beta1 targets the GSK-3beta/beta-catenin pathway via ERK activation in the transition of human lung fibroblasts into myofibroblasts (literal)
- Abstract
- Transforming growth factor-alpha 1 (TGF-beta 1) is known to induce the transition of human lung fibroblasts to myofibroblasts, a primary event in the pathogenesis of idiopathic pulmonary fibrosis. The molecular pathways involved in myofibroblast transformation are only partially identified.
We found that a 24-h treatment with TGF-beta 1 (10 ng/ml) induced alpha-smooth actin (SMA) expression and collagen production in human lung fibroblasts. These effects were abrogated by PD98059, a specific inhibitor of the mitogen-activated protein kinase (MAPK) pathway. TGF-beta 1 treatment activated the MAPK pathway, as shown by an increased phosphorylation of extracellular-regulated kinases (ERK)1/2 after 30 min of exposure. TGF-beta 1 also increased the expression of the Ser-9-phosphorylated inactive form of glycogen synthase kinase-3 beta (GSK-3 beta), an effect that was largely attenuated by PD98059. A nuclear translocation of beta-catenin in human lung fibroblasts was observed 2h after TGF-beta 1 addition both by confocal microscopy and nuclear protein analysis. At this time, TGF-beta 1 also increased the total levels of beta-catenin, an effect that was preventedby PD98059. Similarly to TGF-beta 1, the GSK-3 beta inhibitor lithium chloride (10 mM), increased the total levels of beta-catenin and promoted alpha-SMA expression and collagen production.
This study demonstrates that TGF-beta 1 induces alpha-SMA expression and collagen production in human lung fibroblasts via ERK1/2 activation, GSK-3 beta inhibition and nuclear beta-catenin translocation. The evidence that the silencing of beta-catenin by siRNAs was able to prevent the induction of alpha-SMA expression in TGF-beta 1-treated fibroblasts further supports the hypothesis of a contribution of the GSK-3 beta/beta-catenin pathway in the pathogenesis of idiopathic pulmonary fibrosis. (C) 2008 Elsevier Ltd. All rights reserved. (literal)
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