Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12104/45023
Title: TGF-?1 Up-Regulates the Expression of PDGF-? Receptor mRNA and Induces a Delayed PI3K-, AKT-, and p70S6K-Dependent Proliferative Response in Activated Hepatic Stellate Cells
Author: Torres-Carrillo, N.M.
Torres-Carrillo, N.
Vazquez-Del Mercado, M.
Delgado-Rizo, V.
Oregon-Romero, E.
Parra-Rojas, I.
Munoz-Valle, J.F.
Issue Date: 2008
Abstract: We assessed whether the -844 G/A polymorphism and mRNA expression of plasminogen activator inhibitor 1 (PAI-1) gene are associated with rheumatoid arthritis (RA). Demographic data, hematological, biochemical parameters, disease activity-disability indexes, -844 G/A genotypes and mRNA expression levels of the PAI-1 gene were determined in 50 RA patients and 50 healthy subjects (HS). Non-significant differences in genotype and allele frequencies related to -844 G/A polymorphism in RA versus HS, were found. High mRNA expression of the PAI-1 gene, was demonstrated in RA versus HS (P < 0.05). In addition, A/A genotype carriers showed increase of PAI-1 mRNA expression (3.1-fold) respect to G/G and G/A genotypes in RA patients (P < 0.05). Our finding suggest an association of A/A -844 PAI-1 genotype with high PAI-1 mRNA expression in RA patients. " 2007 Springer-Verlag.",,,,,,"10.1007/s00296-007-0453-z",,,"http://hdl.handle.net/20.500.12104/45023","http://www.scopus.com/inward/record.url?eid=2-s2.0-38049065428&partnerID=40&md5=97a15478100169da337eee9a7d86a49b
MEDLINE",,,,,,"4",,"Rheumatology International",,"355
360",,"28",,"Scopus
WOS
http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&D=med5&AN=17899094",,,,"Index Medicus;Adult;Aged;Arthritis, Rheumatoid/bl [Blood];Arthritis, Rheumatoid/ge [Genetics];Biological Markers/bl [Blood];Case-Control Studies;Female;Gene Frequency;Genetic Predisposition to Disease;Humans;Male;Middle Aged;Phenotype;Plasminogen Activator Inhibitor 1/ge [Genetics];Polymerase Chain Reaction;Polymorphism, Genetic;RNA, Messenger/bl [Blood];Risk Factors;Up-Regulation",,"Plasminogen activator inhibitor-1; Polymorphism; Real-time PCR; Rheumatoid arthritis",,,,,,"The -844 G/A PAI-1 polymorphism is associated with mRNA expression in rheumatoid arthritis",,"Article" "46786","123456789/35008",,"Shah, R., Lipid Research Laboratory, VA Medical Center, Washington, DC, United States, Department of Biochemistry and Molecular Biology, The George Washington University Medical Center, Washington, DC, United States; Reyes-Gordillo, K., Lipid Research Laboratory, VA Medical Center, Washington, DC, United States, Department of Biochemistry and Molecular Biology, The George Washington University Medical Center, Washington, DC, United States; Arellanes-Robledo, J., Lipid Research Laboratory, VA Medical Center, Washington, DC, United States, Department of Biochemistry and Molecular Biology, The George Washington University Medical Center, Washington, DC, United States; Lechuga, C.G., Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, United States, Departamento de Oncología Molecular, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain; Hernández-Nazara, Z., Department of Biochemistry and Molecular Biology, The George Washington University Medical Center, Washington, DC, United States, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, United States, Departamento de Fisiología, Universidad de Guadalajara, Guadalajara, Mexico; Cotty, A., Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, United States; Rojkind, M., Department of Biochemistry and Molecular Biology, The George Washington University Medical Center, Washington, DC, United States, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, United States, Experimental Pathology and Immunology Sections, Department of Clinical Investigation, Walter Reed Army Medical Center, Washington, DC, United States; Lakshman, M.R., Lipid Research Laboratory, VA Medical Center, Washington, DC, United States, Department of Biochemistry and Molecular Biology, The George Washington University Medical Center, Washington, DC, United States",,"Shah, R.
Reyes-Gordillo, K.
Arellanes-Robledo, J.
Lechuga, C.G.
Hernandez-Nazara, Z.
Cotty, A.
Rojkind, M.
Lakshman, M.R.",,"2013",,"Background: Transforming growth factor beta 1 (TGF-?1) is a pleiotropic cytokine that activates hepatic stellate cell (HSC) proliferation, but inhibits parenchymal cell proliferation. Therefore, we hypothesize that TGF-?1 regulates HSC proliferation and elucidated its molecular action. Methods: In order to elucidate the molecular mechanism whereby TGF-?1 up-regulates platelet derived growth factor beta (PDGF-?) receptor mRNA and induces a delayed proliferation of HSC, we used proliferation and apoptosis assays as well as RT-PCR, Western blot analysis, immunostaining, and flow cytometry in mouse and rat HSC. Results: We show that TGF-?1 markedly induces the proliferation of mouse HSC in culture with concomitant 2.1-fold (p &lt; 0.001) stimulation in [3H]-thymidine incorporation into cellular DNA. This induction is maximal between 24 and 36 hours postcytokine exposure that is triggered by 7.6-fold (p &lt; 0.001) up-regulation of PDGF-? receptor mRNA and associated increase in PDGF-? receptor protein after 48 hours. TGF-?1-dependent HSC proliferation is mimicked by H2O2 that is inhibited by catalase, implying that TGF-?1 action is mediated via reactive oxygen species. HSC proliferation is blunted by PDGF-? receptor-neutralizing antibody as well as by specific inhibitors of PI3 kinase (PI3K), AKT, and p70S6K, indicating that the action of TGF-?1 involves the activation of PDGF-? receptor via the PI3K/AKT/p70S6K signaling pathway. TGF-?1 also induces a reorganization of actin and myosin filaments and cell morphology leading to the formation of palisades although their myosin and actin contents remained constant. These findings suggest that TGF-?1-mediated oxidative stress causes the transdifferentiation of HSC and primes them for extracellular matrix (ECM) deposition and scar contraction. Conclusions: We conclude that liver injury up-regulates TGF-?1 that inhibits parenchymal cell proliferation, but stimulates HSC proliferation leading to the production of ECM and type I collagen resulting in fibrosis. " 2013 by the Research Society on Alcoholism.
URI: http://hdl.handle.net/20.500.12104/45007
http://www.scopus.com/inward/record.url?eid=2-s2.0-84886380249&partnerID=40&md5=45bcab84503192dca0b927d4b8c59930
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