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Cells 2018, 7(9), 142; https://doi.org/10.3390/cells7090142

Platelet-Rich Plasma Prevents In Vitro Transforming Growth Factor-β1-Induced Fibroblast to Myofibroblast Transition: Involvement of Vascular Endothelial Growth Factor (VEGF)-A/VEGF Receptor-1-Mediated Signaling

1
Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, 50134 Florence, Italy
2
Transfusion Medicine and Cell Therapy Unit, ”A. Meyer” University Children’s Hospital, 50139 Florence, Italy
This paper is dedicated to the dear memory of Lucia Formigli who passed away on 18 March 2014.
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 31 July 2018 / Revised: 14 September 2018 / Accepted: 16 September 2018 / Published: 19 September 2018
(This article belongs to the Special Issue Tissue Regeneration and Fibrosis)
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Abstract

The antifibrotic potential of platelet-rich plasma (PRP) is controversial. This study examined the effects of PRP on in vitro transforming growth factor (TGF)-β1-induced differentiation of fibroblasts into myofibroblasts, the main drivers of fibrosis, and the involvement of vascular endothelial growth factor (VEGF)-A in mediating PRP-induced responses. The impact of PRP alone on fibroblast differentiation was also assessed. Myofibroblastic phenotype was evaluated by confocal fluorescence microscopy and western blotting analyses of α-smooth muscle actin (sma) and type-1 collagen expression, vinculin-rich focal adhesion clustering, and stress fiber assembly. Notch-1, connexin 43, and VEGF-A expression were also analyzed by RT-PCR. PRP negatively regulated fibroblast-myofibroblast transition via VEGF-A/VEGF receptor (VEGFR)-1-mediated inhibition of TGF-β1/Smad3 signaling. Indeed TGF-β1/PRP co-treated fibroblasts showed a robust attenuation of the myofibroblastic phenotype concomitant with a decrease of Smad3 expression levels. The VEGFR-1 inhibition by KRN633 or blocking antibodies, or VEGF-A neutralization in these cells prevented the PRP-promoted effects. Moreover PRP abrogated the TGF-β1-induced reduction of VEGF-A and VEGFR-1 cell expression. The role of VEGF-A signaling in counteracting myofibroblast generation was confirmed by cell treatment with soluble VEGF-A. PRP as single treatment did not induce fibroblast myodifferentiation. This study provides new insights into cellular and molecular mechanisms underpinning PRP antifibrotic action. View Full-Text
Keywords: myofibroblasts; fibrosis; platelet-rich plasma (PRP); vascular endothelial growth factor (VEGF)-A; VEGFR-1/flt-1; Notch-1; transforming growth factor (TGF)-β1/Smad3; α-smooth muscle actin; Connexin 43; confocal immunofluorescence myofibroblasts; fibrosis; platelet-rich plasma (PRP); vascular endothelial growth factor (VEGF)-A; VEGFR-1/flt-1; Notch-1; transforming growth factor (TGF)-β1/Smad3; α-smooth muscle actin; Connexin 43; confocal immunofluorescence
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Chellini, F.; Tani, A.; Vallone, L.; Nosi, D.; Pavan, P.; Bambi, F.; Zecchi Orlandini, S.; Sassoli, C. Platelet-Rich Plasma Prevents In Vitro Transforming Growth Factor-β1-Induced Fibroblast to Myofibroblast Transition: Involvement of Vascular Endothelial Growth Factor (VEGF)-A/VEGF Receptor-1-Mediated Signaling . Cells 2018, 7, 142.

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