Fibronectin glycation increases IGF-I induced proliferation of human aortic smooth muscle cells

Maria Lúcia Corrêa-Giannella, Maria Regina Andrade De Azevedo, Derek Leroith, Daniel Giannella-Neto

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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.

Original languageEnglish
Article number19
JournalDiabetology and Metabolic Syndrome
Issue number1
StatePublished - 2012


  • Advanced glycation end products (AGE)
  • Diabetes mellitus
  • IGF-I
  • IGFBP-4
  • PDGF
  • Smooth muscle cells


Dive into the research topics of 'Fibronectin glycation increases IGF-I induced proliferation of human aortic smooth muscle cells'. Together they form a unique fingerprint.

Cite this