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

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 l...

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Autores principales:	Valentina Bizzarro, Bianca Fontanella, Anna Carratù, Raffaella Belvedere, Raffaele Marfella, Luca Parente, Antonello Petrella
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/00523a017c814675a89720e43636e579
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spelling	oai:doaj.org-article:00523a017c814675a89720e43636e5792021-11-18T07:04:33ZAnnexin A1 N-terminal derived peptide Ac2-26 stimulates fibroblast migration in high glucose conditions.1932-620310.1371/journal.pone.0045639https://doaj.org/article/00523a017c814675a89720e43636e5792012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23029153/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Deficient 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.Valentina BizzarroBianca FontanellaAnna CarratùRaffaella BelvedereRaffaele MarfellaLuca ParenteAntonello PetrellaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e45639 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Valentina Bizzarro Bianca Fontanella Anna Carratù Raffaella Belvedere Raffaele Marfella Luca Parente Antonello Petrella Annexin A1 N-terminal derived peptide Ac2-26 stimulates fibroblast migration in high glucose conditions.
description	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.
format	article
author	Valentina Bizzarro Bianca Fontanella Anna Carratù Raffaella Belvedere Raffaele Marfella Luca Parente Antonello Petrella
author_facet	Valentina Bizzarro Bianca Fontanella Anna Carratù Raffaella Belvedere Raffaele Marfella Luca Parente Antonello Petrella
author_sort	Valentina Bizzarro
title	Annexin A1 N-terminal derived peptide Ac2-26 stimulates fibroblast migration in high glucose conditions.
title_short	Annexin A1 N-terminal derived peptide Ac2-26 stimulates fibroblast migration in high glucose conditions.
title_full	Annexin A1 N-terminal derived peptide Ac2-26 stimulates fibroblast migration in high glucose conditions.
title_fullStr	Annexin A1 N-terminal derived peptide Ac2-26 stimulates fibroblast migration in high glucose conditions.
title_full_unstemmed	Annexin A1 N-terminal derived peptide Ac2-26 stimulates fibroblast migration in high glucose conditions.
title_sort	annexin a1 n-terminal derived peptide ac2-26 stimulates fibroblast migration in high glucose conditions.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/00523a017c814675a89720e43636e579
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Annexin A1 N-terminal derived peptide Ac2-26 stimulates fibroblast migration in high glucose conditions.

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