HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Summary Full Text Full Text (PDF) All Versions of this Article: fj.06-6104fjev1 20/13/2402    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Giacco, F. Articles by Formisano, P. Search for Related Content PubMed PubMed Citation Articles by Giacco, F. Articles by Formisano, P.

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^* and Pietro Formisano^*,1

^* Dipartimento di Biologia e Patologia Cellulare e Molecolare and Istituto di Endocrinologia ed Oncologia Sperimentale del CNR; and

Dipartimento di Medicina Clinica e Sperimentale, Università di Napoli "Federico II", Napoli, Italy

¹Correspondence: Dipartimento di Biologia e Patologia Cellulare e Molecolare "L. Califano" Università di Napoli "Federico II" Via Pansini 5, 80131 Napoli, Italy. E-mail: fpietro{at}unina.it

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

This article has been cited by other articles:

				T. Ide, Y. Kitajima, A. Miyoshi, T. Ohtsuka, M. Mitsuno, K. Ohtaka, and K. Miyazaki The Hypoxic Environment in Tumor-Stromal Cells Accelerates Pancreatic Cancer Progression via the Activation of Paracrine Hepatocyte Growth Factor/c-Met Signaling Ann. Surg. Oncol., September 1, 2007; 14(9): 2600 - 2607. [Abstract] [Full Text] [PDF]

				A. T. Nurden Platelets and Tissue Remodeling: Extending the Role of the Blood Clotting System Endocrinology, July 1, 2007; 148(7): 3053 - 3055. [Full Text] [PDF]