Fibronectin glycation increases IGF-I induced proliferation of human aortic smooth muscle cells
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
23/10/2013
23/10/2013
2012
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Resumo |
The advanced glycation end products, namely AGEs, contribute to long-termed complications of diabetes mellitus, including macroangiopathy, where smooth muscle cells (SMC) proliferation stimulated by platelet-derived growth factor (PDGF) isoforms and insulin-like growth factor-I (IGF-I) plays an important role. The objective of the present study was to investigate the effect of an AGE-modified extracellular matrix protein on IGF-I induced SMC proliferation and on the IGF-I-IGF binding protein 4 (IGFBP-4) axis under basal conditions and after stimulation with PDGF-BB. IGF-I resulted in significantly higher thymidine incorporation in SMC seeded on AGE-modified fibronectin (AGE-FN) in comparison to cells seeded on fibronectin (FN). This augmented proliferation could not be accounted for by increased expression of IGF-IR, by decreased secretion of IGFBP-4, a binding protein that inhibits IGF-I mitogenic effects or by increased IGF-IR autophosphorylation. PDGF-BB did not modulate IGF-IR and IGFBP-4 mRNA expression in any of the substrata, however, this growth factor elicited opposite effects on the IGFBP-4 content in the conditioned media, increasing it in cells plated on FN and diminishing it in cells plated on AGE-FN. These findings suggest that one mechanism by which AGE-modified proteins is involved in the pathogenesis of diabetes-associated atherosclerosis might be by increasing SMC susceptibility to IGF-I mitogenic effects. FAPESP, Sao Paulo, Brazil [91/3617-8] FAPESP (Sao Paulo, Brazil) |
Identificador |
DIABETOLOGY & METABOLIC SYNDROME, LONDON, v. 4, pp. 209-215, MAY 3, 2012 1758-5996 http://www.producao.usp.br/handle/BDPI/35758 10.1186/1758-5996-4-19 |
Idioma(s) |
eng |
Publicador |
BIOMED CENTRAL LTD LONDON |
Relação |
DIABETOLOGY & METABOLIC SYNDROME |
Direitos |
openAccess Copyright BIOMED CENTRAL LTD |
Palavras-Chave | #DIABETES MELLITUS #ADVANCED GLYCATION END PRODUCTS (AGE) #SMOOTH MUSCLE CELLS #PDGF #IGF-I #IGFBP-4 #GROWTH-FACTOR-I #FACTOR-BINDING PROTEIN-4 #GLYCOSYLATION END-PRODUCTS #GENE-EXPRESSION #NONENZYMATIC GLYCOSYLATION #DIABETIC ATHEROSCLEROSIS #DIFFERENTIAL EXPRESSION #SIGNALING PATHWAYS #CORONARY-ARTERY #A EXPRESSION #ENDOCRINOLOGY & METABOLISM |
Tipo |
article original article publishedVersion |