Annexin A1 N-terminal derived peptide Ac2-26 stimulates fibroblast migration in high glucose conditions

PLoS One. 2012;7(9):e45639. doi: 10.1371/journal.pone.0045639. Epub 2012 Sep 21.


Deficient wound healing in diabetic patients is very frequent, but the cellular and molecular causes are poorly defined. In this study, we have evaluated whether Annexin A1 derived peptide Ac2-26 stimulates fibroblast migration in high glucose conditions. Using normal human skin fibroblasts WS1 in low glucose (LG) or high glucose (HG) we observed the enrichment of Annexin A1 protein at cell movement structures like lamellipodial extrusions and interestingly, a significant decrease in levels of the protein in HG conditions. The analysis of the translocation of Annexin A1 to cell membrane showed lower levels of Annexin A1 in both membrane pool and supernatants of WS1 cells treated with HG. Wound-healing assays using cell line transfected with Annexin A1 siRNAs indicated a slowing down in migration speed of cells suggesting that Annexin A1 has a role in the migration of WS1 cells. In order to analyze the role of extracellular Annexin A1 in cell migration, we have performed wound-healing assays using Ac2-26 showing that peptide was able to increase fibroblast cell migration in HG conditions. Experiments on the mobilization of intracellular calcium and analysis of p-ERK expression confirmed the activity of the FPR1 following stimulation with the peptide Ac2-26. A wound-healing assay on WS1 cells in the presence of the FPR agonist fMLP, of the FPR antagonist CsH and in the presence of Ac2-26 indicated that Annexin A1 influences fibroblast cell migration under HG conditions acting through FPR receptors whose expression was slightly increased in HG. In conclusion, these data demonstrate that (i) Annexin A1 is involved in migration of WS1 cells, through interaction with FPRs; (ii) N- terminal peptide of Annexin A1 Ac2-26 is able to stimulate direct migration of WS1 cells in high glucose treatment possibly due to the increased receptor expression observed in hyperglycemia conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Annexin A1 / chemistry*
  • Annexin A1 / pharmacology
  • Calcium Signaling
  • Cell Movement / drug effects*
  • Cells, Cultured
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Flow Cytometry
  • Glucose / administration & dosage*
  • Humans
  • Peptides / pharmacology*


  • Annexin A1
  • Peptides
  • annexin A1 peptide (2-26)
  • Glucose

Grants and funding

The work conducted in the authors’ laboratory and referred to in this paper was funded by University of Salerno (FARB 2009, 2010, 2011), from BCC, Banca di Credito Cooperativo, Fisciano (Salerno), from Fondazione con il Sud, and from Regione Campania. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.