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 †
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 endothe...
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doaj-43fe46b6b87a4c74ac4b5339348317602020-11-25T00:32:14ZengMDPI AGCells2073-44092018-09-017914210.3390/cells7090142cells7090142Platelet-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 †Flaminia Chellini0Alessia Tani1Larissa Vallone2Daniele Nosi3Paola Pavan4Franco Bambi5Sandra Zecchi Orlandini6Chiara Sassoli7Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, 50134 Florence, ItalyDepartment of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, 50134 Florence, ItalyDepartment of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, 50134 Florence, ItalyDepartment of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, 50134 Florence, ItalyTransfusion Medicine and Cell Therapy Unit, ”A. Meyer” University Children’s Hospital, 50139 Florence, ItalyTransfusion Medicine and Cell Therapy Unit, ”A. Meyer” University Children’s Hospital, 50139 Florence, ItalyDepartment of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, 50134 Florence, ItalyDepartment of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, 50134 Florence, ItalyThe 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.http://www.mdpi.com/2073-4409/7/9/142myofibroblastsfibrosisplatelet-rich plasma (PRP)vascular endothelial growth factor (VEGF)-AVEGFR-1/flt-1Notch-1transforming growth factor (TGF)-β1/Smad3α-smooth muscle actinConnexin 43confocal immunofluorescence |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Flaminia Chellini Alessia Tani Larissa Vallone Daniele Nosi Paola Pavan Franco Bambi Sandra Zecchi Orlandini Chiara Sassoli |
spellingShingle |
Flaminia Chellini Alessia Tani Larissa Vallone Daniele Nosi Paola Pavan Franco Bambi Sandra Zecchi Orlandini Chiara Sassoli 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 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 |
author_facet |
Flaminia Chellini Alessia Tani Larissa Vallone Daniele Nosi Paola Pavan Franco Bambi Sandra Zecchi Orlandini Chiara Sassoli |
author_sort |
Flaminia Chellini |
title |
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 † |
title_short |
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 † |
title_full |
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 † |
title_fullStr |
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 † |
title_full_unstemmed |
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 † |
title_sort |
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 † |
publisher |
MDPI AG |
series |
Cells |
issn |
2073-4409 |
publishDate |
2018-09-01 |
description |
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. |
topic |
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 |
url |
http://www.mdpi.com/2073-4409/7/9/142 |
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