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The Combination of Synoeca-MP Antimicrobial Peptide with IDR-1018 Stimulates Proliferation, Migration, and the Expression of Pro-Regenerative Genes in Both Human Skin Cell Cultures and 3D Skin Equivalents

In skin lesions, the development of microbial infection affects the healing process, increasing morbidity and mortality rates in patients with severe burns, diabetic foot, and other types of skin injuries. Synoeca-MP is an antimicrobial peptide (AMP) that exhibits activity against several bacteria o...

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Autores principales: Alencar-Silva, Thuany, Díaz-Martín, Rubén D., Zonari, Alessandra, Foyt, Daniel, Guiang, Mylieneth, Pogue, Robert, Saldanha-Araujo, Felipe, Dias, Simoni Campos, Franco, Octavio Luiz, Carvalho, Juliana Lott
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10216143/
https://www.ncbi.nlm.nih.gov/pubmed/37238674
http://dx.doi.org/10.3390/biom13050804
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author Alencar-Silva, Thuany
Díaz-Martín, Rubén D.
Zonari, Alessandra
Foyt, Daniel
Guiang, Mylieneth
Pogue, Robert
Saldanha-Araujo, Felipe
Dias, Simoni Campos
Franco, Octavio Luiz
Carvalho, Juliana Lott
author_facet Alencar-Silva, Thuany
Díaz-Martín, Rubén D.
Zonari, Alessandra
Foyt, Daniel
Guiang, Mylieneth
Pogue, Robert
Saldanha-Araujo, Felipe
Dias, Simoni Campos
Franco, Octavio Luiz
Carvalho, Juliana Lott
author_sort Alencar-Silva, Thuany
collection PubMed
description In skin lesions, the development of microbial infection affects the healing process, increasing morbidity and mortality rates in patients with severe burns, diabetic foot, and other types of skin injuries. Synoeca-MP is an antimicrobial peptide (AMP) that exhibits activity against several bacteria of clinical importance, but its cytotoxicity can represent a problem for its positioning as an effective antimicrobial compound. In contrast, the immunomodulatory peptide IDR-1018 presents low toxicity and a wide regenerative potential due to its ability to reduce apoptotic mRNA expression and promote skin cell proliferation. In the present study, we used human skin cells and a 3D skin equivalent models to analyze the potential of the IDR-1018 peptide to attenuate the cytotoxicity of synoeca-MP, as well as the influence of synoeca-MP/IDR-1018 combination on cell proliferation, regenerative processes, and wound repair. We found that the addition of IDR-1018 significantly improved the biological properties of synoeca-MP on skin cells without modifying its antibacterial activity against S. aureus. Likewise, in both melanocytes and keratinocytes, the treatment with synoeca-MP/IDR-1018 combination induces cell proliferation and migration, while in a 3D human skin equivalent model, it can accelerate wound reepithelization. Furthermore, treatment with this peptide combination generates an up-regulation in the expression of pro-regenerative genes in both monolayer cell cultures and in 3D skin equivalents. This data suggests that the synoeca-MP/IDR-1018 combination possesses a good profile of antimicrobial and pro-regenerative activity, opening the door to the development of new strategies for the treatment of skin lesions.
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spelling pubmed-102161432023-05-27 The Combination of Synoeca-MP Antimicrobial Peptide with IDR-1018 Stimulates Proliferation, Migration, and the Expression of Pro-Regenerative Genes in Both Human Skin Cell Cultures and 3D Skin Equivalents Alencar-Silva, Thuany Díaz-Martín, Rubén D. Zonari, Alessandra Foyt, Daniel Guiang, Mylieneth Pogue, Robert Saldanha-Araujo, Felipe Dias, Simoni Campos Franco, Octavio Luiz Carvalho, Juliana Lott Biomolecules Article In skin lesions, the development of microbial infection affects the healing process, increasing morbidity and mortality rates in patients with severe burns, diabetic foot, and other types of skin injuries. Synoeca-MP is an antimicrobial peptide (AMP) that exhibits activity against several bacteria of clinical importance, but its cytotoxicity can represent a problem for its positioning as an effective antimicrobial compound. In contrast, the immunomodulatory peptide IDR-1018 presents low toxicity and a wide regenerative potential due to its ability to reduce apoptotic mRNA expression and promote skin cell proliferation. In the present study, we used human skin cells and a 3D skin equivalent models to analyze the potential of the IDR-1018 peptide to attenuate the cytotoxicity of synoeca-MP, as well as the influence of synoeca-MP/IDR-1018 combination on cell proliferation, regenerative processes, and wound repair. We found that the addition of IDR-1018 significantly improved the biological properties of synoeca-MP on skin cells without modifying its antibacterial activity against S. aureus. Likewise, in both melanocytes and keratinocytes, the treatment with synoeca-MP/IDR-1018 combination induces cell proliferation and migration, while in a 3D human skin equivalent model, it can accelerate wound reepithelization. Furthermore, treatment with this peptide combination generates an up-regulation in the expression of pro-regenerative genes in both monolayer cell cultures and in 3D skin equivalents. This data suggests that the synoeca-MP/IDR-1018 combination possesses a good profile of antimicrobial and pro-regenerative activity, opening the door to the development of new strategies for the treatment of skin lesions. MDPI 2023-05-09 /pmc/articles/PMC10216143/ /pubmed/37238674 http://dx.doi.org/10.3390/biom13050804 Text en © 2023 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
Alencar-Silva, Thuany
Díaz-Martín, Rubén D.
Zonari, Alessandra
Foyt, Daniel
Guiang, Mylieneth
Pogue, Robert
Saldanha-Araujo, Felipe
Dias, Simoni Campos
Franco, Octavio Luiz
Carvalho, Juliana Lott
The Combination of Synoeca-MP Antimicrobial Peptide with IDR-1018 Stimulates Proliferation, Migration, and the Expression of Pro-Regenerative Genes in Both Human Skin Cell Cultures and 3D Skin Equivalents
title The Combination of Synoeca-MP Antimicrobial Peptide with IDR-1018 Stimulates Proliferation, Migration, and the Expression of Pro-Regenerative Genes in Both Human Skin Cell Cultures and 3D Skin Equivalents
title_full The Combination of Synoeca-MP Antimicrobial Peptide with IDR-1018 Stimulates Proliferation, Migration, and the Expression of Pro-Regenerative Genes in Both Human Skin Cell Cultures and 3D Skin Equivalents
title_fullStr The Combination of Synoeca-MP Antimicrobial Peptide with IDR-1018 Stimulates Proliferation, Migration, and the Expression of Pro-Regenerative Genes in Both Human Skin Cell Cultures and 3D Skin Equivalents
title_full_unstemmed The Combination of Synoeca-MP Antimicrobial Peptide with IDR-1018 Stimulates Proliferation, Migration, and the Expression of Pro-Regenerative Genes in Both Human Skin Cell Cultures and 3D Skin Equivalents
title_short The Combination of Synoeca-MP Antimicrobial Peptide with IDR-1018 Stimulates Proliferation, Migration, and the Expression of Pro-Regenerative Genes in Both Human Skin Cell Cultures and 3D Skin Equivalents
title_sort combination of synoeca-mp antimicrobial peptide with idr-1018 stimulates proliferation, migration, and the expression of pro-regenerative genes in both human skin cell cultures and 3d skin equivalents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10216143/
https://www.ncbi.nlm.nih.gov/pubmed/37238674
http://dx.doi.org/10.3390/biom13050804
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