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Enhanced Platelet-Rich Plasma (ePRP) Stimulates Wound Healing through Effects on Metabolic Reprogramming in Fibroblasts
As a source of growth factors for expediting wound healing and tissue regeneration, plasma-rich plasma (PRP) has been extensively applied in diverse fields including orthopaedics, ophthalmology, oral and maxillofacial surgery, dentistry, and gynaecology. However, the function of PRP in metabolic reg...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657780/ https://www.ncbi.nlm.nih.gov/pubmed/34884429 http://dx.doi.org/10.3390/ijms222312623 |
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author | Weng, Hsin-Pei Cheng, Yuan-Yang Lee, Hsin-Lun Hsu, Tai-Yi Chang, Yu-Tang Shen, Yao-An |
author_facet | Weng, Hsin-Pei Cheng, Yuan-Yang Lee, Hsin-Lun Hsu, Tai-Yi Chang, Yu-Tang Shen, Yao-An |
author_sort | Weng, Hsin-Pei |
collection | PubMed |
description | As a source of growth factors for expediting wound healing and tissue regeneration, plasma-rich plasma (PRP) has been extensively applied in diverse fields including orthopaedics, ophthalmology, oral and maxillofacial surgery, dentistry, and gynaecology. However, the function of PRP in metabolic regulations remains enigmatic. A standardized method was devised herein to enrich growth factors and to lyophilize it as enhanced PRP (ePRP) powder, which could become ubiquitously available without mechanical centrifugation in clinical practice. To identify metabolic reprogramming in human dermal fibroblasts under ePRP treatment, putative metabolic targets were identified by transcriptome profiling and validated for their metabolic effects and mechanism. ePRP does not only promote wound healing but re-aligns energy metabolism by shifting to glycolysis through stimulation of glycolytic enzyme activity in fibroblasts. On the contrary, oxygen consumption rates and several mitochondrial respiration activities were attenuated in ePRP-treated fibroblasts. Furthermore, ePRP treatment drives the mitochondrial resetting by hindering the mitochondrial biogenesis-related genes and results in a dampened mitochondrial mass. Antioxidant production was further increased by ePRP treatment to prevent reactive oxygen species formation. Besides, ePRP also halts the senescence progression of fibroblasts by activating SIRT1 expression. Importantly, the glycolytic inhibitor 2-DG can completely reverse the ePRP-enhanced wound healing capacity, whereas the mitochondrial inhibitor oligomycin cannot. This is the first study to utilize PRP for comprehensively investigating its effects on the metabolic reprogramming of fibroblasts. These findings indicate that PRP’s primary metabolic regulation is to promote metabolic reprogramming toward glycolytic energy metabolism in fibroblasts, preserving redox equilibrium and allowing anabolic pathways necessary for the healing and anti-ageing process. |
format | Online Article Text |
id | pubmed-8657780 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86577802021-12-10 Enhanced Platelet-Rich Plasma (ePRP) Stimulates Wound Healing through Effects on Metabolic Reprogramming in Fibroblasts Weng, Hsin-Pei Cheng, Yuan-Yang Lee, Hsin-Lun Hsu, Tai-Yi Chang, Yu-Tang Shen, Yao-An Int J Mol Sci Article As a source of growth factors for expediting wound healing and tissue regeneration, plasma-rich plasma (PRP) has been extensively applied in diverse fields including orthopaedics, ophthalmology, oral and maxillofacial surgery, dentistry, and gynaecology. However, the function of PRP in metabolic regulations remains enigmatic. A standardized method was devised herein to enrich growth factors and to lyophilize it as enhanced PRP (ePRP) powder, which could become ubiquitously available without mechanical centrifugation in clinical practice. To identify metabolic reprogramming in human dermal fibroblasts under ePRP treatment, putative metabolic targets were identified by transcriptome profiling and validated for their metabolic effects and mechanism. ePRP does not only promote wound healing but re-aligns energy metabolism by shifting to glycolysis through stimulation of glycolytic enzyme activity in fibroblasts. On the contrary, oxygen consumption rates and several mitochondrial respiration activities were attenuated in ePRP-treated fibroblasts. Furthermore, ePRP treatment drives the mitochondrial resetting by hindering the mitochondrial biogenesis-related genes and results in a dampened mitochondrial mass. Antioxidant production was further increased by ePRP treatment to prevent reactive oxygen species formation. Besides, ePRP also halts the senescence progression of fibroblasts by activating SIRT1 expression. Importantly, the glycolytic inhibitor 2-DG can completely reverse the ePRP-enhanced wound healing capacity, whereas the mitochondrial inhibitor oligomycin cannot. This is the first study to utilize PRP for comprehensively investigating its effects on the metabolic reprogramming of fibroblasts. These findings indicate that PRP’s primary metabolic regulation is to promote metabolic reprogramming toward glycolytic energy metabolism in fibroblasts, preserving redox equilibrium and allowing anabolic pathways necessary for the healing and anti-ageing process. MDPI 2021-11-23 /pmc/articles/PMC8657780/ /pubmed/34884429 http://dx.doi.org/10.3390/ijms222312623 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Weng, Hsin-Pei Cheng, Yuan-Yang Lee, Hsin-Lun Hsu, Tai-Yi Chang, Yu-Tang Shen, Yao-An Enhanced Platelet-Rich Plasma (ePRP) Stimulates Wound Healing through Effects on Metabolic Reprogramming in Fibroblasts |
title | Enhanced Platelet-Rich Plasma (ePRP) Stimulates Wound Healing through Effects on Metabolic Reprogramming in Fibroblasts |
title_full | Enhanced Platelet-Rich Plasma (ePRP) Stimulates Wound Healing through Effects on Metabolic Reprogramming in Fibroblasts |
title_fullStr | Enhanced Platelet-Rich Plasma (ePRP) Stimulates Wound Healing through Effects on Metabolic Reprogramming in Fibroblasts |
title_full_unstemmed | Enhanced Platelet-Rich Plasma (ePRP) Stimulates Wound Healing through Effects on Metabolic Reprogramming in Fibroblasts |
title_short | Enhanced Platelet-Rich Plasma (ePRP) Stimulates Wound Healing through Effects on Metabolic Reprogramming in Fibroblasts |
title_sort | enhanced platelet-rich plasma (eprp) stimulates wound healing through effects on metabolic reprogramming in fibroblasts |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657780/ https://www.ncbi.nlm.nih.gov/pubmed/34884429 http://dx.doi.org/10.3390/ijms222312623 |
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