Galectin-3 expression in macrophages is signaled by Ras/MAP kinase pathway and up-regulated by modified lipoproteins

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dc.contributor.authorKoanhoi Kim-
dc.contributor.authorE P Mayer-
dc.contributor.authorM Nachtigal-
dc.date.accessioned2017-04-19T09:00:24Z-
dc.date.available2017-04-19T09:00:24Z-
dc.date.issued2003-
dc.identifier.issn0167-4889-
dc.identifier.uri10.1016/S0167-4889(03)00045-4ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/6271-
dc.description.abstractTo study the signaling pathway involved in the regulation of galectin-3 expression we used phorbol ester to stimulate macrophage differentiation of THP-1 cells. Treatment with phorbol 12-myristate 13-acetate (PMA) increased significantly the level of expression of galectin-3 in THP-1 cells. PMA-induced galectin-3 overexpression was blocked by: protein kinase C inhibitors staurosporine, calphostin C, and apigenin; tyrosine-specific protein kinase inhibitors genistein and tyrphostin A25; PD 98059, a selective inhibitor of mitogen-activated protein kinase (MAPK) kinase 1 (MEK1 or MKK1); and SB 203580, a specific inhibitor of p38 MAPK. Galectin-3 up-regulation was not affected by exposure to two inhibitors of cAMP-dependent protein kinase (PKA), H-89 and KT5720. Co-transfection of pPG3.5, a plasmid vector containing the rabbit galectin-3 promoter and the constructs pMCL-MKK1 N3 or pRC-RSV-MKK3Glu that constitutively express MKK1 and MKK3, raised the activity of galectin-3 promoter by 185% and 110%, respectively. Co-transfection with a Ha-Ras expression vector stimulated galectin-3 promoter activity approximately 10-fold. Expression of c-Jun or v-Jun raised the level of galectin-3 promoter activity more the three- and fourfold, respectively. Co-transfection of c-Jun and pPG3.5 5′-upstream deletion mutants resulted in a reduction of the galectin-3 promoter activity by 50% to 80%. Transfection of c-Jun, v-Jun or Ha-Ras increased significantly galectin-3 protein in THP-1 cells. These findings indicated that Ras/MEKK1/MKK1-dependent/AP-1 signal transduction pathway plays an important role in the expression of galectin-3 in PMA-stimulated macrophages. We further investigated the effect of modified lipoproteins on galectin-3 expression in macrophages. Murine resident peritoneal macrophages loaded with acetylated low-density lipoprotein (AcLDL) or oxidized LDL (OxLDL) showed increased galectin-3 protein and mRNA. These results showed that treatment of macrophages with PMA or modified lipoproteins results in galectin-3 overexpression. These findings may explain the enhanced expression of galectin-3 in atherosclerotic foam cells and suggest that Ras/MAPK signal transduction pathway is involved in controlling this gene.-
dc.publisherElsevier-
dc.titleGalectin-3 expression in macrophages is signaled by Ras/MAP kinase pathway and up-regulated by modified lipoproteins-
dc.title.alternativeGalectin-3 expression in macrophages is signaled by Ras/MAP kinase pathway and up-regulated by modified lipoproteins-
dc.typeArticle-
dc.citation.titleBiochimica et Biophysica Acta-Molecular Cell Research-
dc.citation.number1-
dc.citation.endPage23-
dc.citation.startPage13-
dc.citation.volume1641-
dc.contributor.affiliatedAuthorKoanhoi Kim-
dc.contributor.alternativeName김관회-
dc.contributor.alternativeNameMayer-
dc.contributor.alternativeNameNachtigal-
dc.identifier.bibliographicCitationBiochimica et Biophysica Acta-Molecular Cell Research, vol. 1641, no. 1, pp. 13-23-
dc.identifier.doi10.1016/S0167-4889(03)00045-4-
dc.subject.keywordGalectin-3-
dc.subject.keywordJun-
dc.subject.keywordLipoprotein-
dc.subject.keywordMAP kinase-
dc.subject.keywordProtein kinase-
dc.subject.keywordRas-
dc.subject.localGalectin-3-
dc.subject.localgalectin-3-
dc.subject.localJun-
dc.subject.localLipoproteins-
dc.subject.locallipoprotein-
dc.subject.localLipoprotein-
dc.subject.locallipoproteins-
dc.subject.localMAP kinases-
dc.subject.localmap kinase-
dc.subject.localMAP kinase-
dc.subject.localProtein kinase-
dc.subject.localRAS-
dc.subject.localRas-
dc.subject.localras-
dc.description.journalClassY-
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