Thrombin-activated platelets induce proliferation of human skin fibroblasts by stimulating autocrine production of insulin-like growth factor-1.

Ferdinando Giacco, Giuseppe Perruolo, Elio D'Agostino, Giorgio Fratellanza, Enzo Perna, Saverio Misso, Gennaro Saldalamacchia, Francesco Oriente, Francesca Fiory, Claudia Miele, Salvatore Formisano, Francesco Beguinot, Pietro Formisano

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Platelet components have found successful clinical utilization to initiate or to accelerate tissue-repair mechanisms. However, the molecular pathways by which platelet factors contribute to tissue regeneration have not been fully elucidated. We have studied the effect of thrombin-activated platelets (TAPs) on cell growth in vivo and in cultured cell systems. Application of TAPs to ulcerative skin lesions of diabetic patients induced local activation of ERK1/2 and Akt/PKB. Moreover, when applied to cultured human skin fibroblasts, TAPs promoted cell growth and DNA synthesis and activated platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF)-1 receptor tyrosine kinases. PDGF was released by TAPs and rapidly achieved a plateau. At variance, the release of IGF-1 was mainly provided by the TAPs-stimulated fibroblasts and progressively increased up to 48 h. The PDGF-R blocker Ag1296 reduced the activation of Akt/PKB and, at a lesser extent, of ERK1/2. Conversely, inhibition of IGF-1 signaling by Ag1024 and expression of a dominant-negative IGF-1R mutant selectively reduced the stimulation of ERK1/2 by TAPs and fibroblast-released factors, with minor changes of Akt/PKB activity. Thus, platelet factors promote fibroblast growth by acutely activating Akt/PKB and ERK1/2. Sustained activation of ERK1/2, however, requires autocrine production of IGF-1 by TAPs-stimulated fibroblasts.

Original languageEnglish (US)
Pages (from-to)2402-2404
Number of pages3
JournalThe FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume20
Issue number13
DOIs
StatePublished - Nov 2006
Externally publishedYes

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Somatomedins
Fibroblasts
Platelets
Thrombin
Skin
Blood Platelets
Platelet-Derived Growth Factor
Chemical activation
Cell growth
Somatomedin Receptors
Tissue regeneration
Fibroblast Growth Factors
Receptor Protein-Tyrosine Kinases
Growth
Protein-Tyrosine Kinases
Regeneration
Cultured Cells
Repair
Cells
Tissue

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Thrombin-activated platelets induce proliferation of human skin fibroblasts by stimulating autocrine production of insulin-like growth factor-1. / Giacco, Ferdinando; Perruolo, Giuseppe; D'Agostino, Elio; Fratellanza, Giorgio; Perna, Enzo; Misso, Saverio; Saldalamacchia, Gennaro; Oriente, Francesco; Fiory, Francesca; Miele, Claudia; Formisano, Salvatore; Beguinot, Francesco; Formisano, Pietro.

In: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 20, No. 13, 11.2006, p. 2402-2404.

Research output: Contribution to journalArticle

Giacco, F, Perruolo, G, D'Agostino, E, Fratellanza, G, Perna, E, Misso, S, Saldalamacchia, G, Oriente, F, Fiory, F, Miele, C, Formisano, S, Beguinot, F & Formisano, P 2006, 'Thrombin-activated platelets induce proliferation of human skin fibroblasts by stimulating autocrine production of insulin-like growth factor-1.', The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, vol. 20, no. 13, pp. 2402-2404. https://doi.org/10.1096/fj.06-6104fje
Giacco, Ferdinando ; Perruolo, Giuseppe ; D'Agostino, Elio ; Fratellanza, Giorgio ; Perna, Enzo ; Misso, Saverio ; Saldalamacchia, Gennaro ; Oriente, Francesco ; Fiory, Francesca ; Miele, Claudia ; Formisano, Salvatore ; Beguinot, Francesco ; Formisano, Pietro. / Thrombin-activated platelets induce proliferation of human skin fibroblasts by stimulating autocrine production of insulin-like growth factor-1. In: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2006 ; Vol. 20, No. 13. pp. 2402-2404.
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AU - Fratellanza, Giorgio

AU - Perna, Enzo

AU - Misso, Saverio

AU - Saldalamacchia, Gennaro

AU - Oriente, Francesco

AU - Fiory, Francesca

AU - Miele, Claudia

AU - Formisano, Salvatore

AU - Beguinot, Francesco

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