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Amniotic Membrane Modifies the Genetic Program Induced by TGFß, Stimulating Keratinocyte Proliferation and Migration in Chronic Wounds
BACKGROUND: Post-traumatic large-surface or deep wounds often cannot progress to reepithelialisation because they become irresponsive in the inflammatory stage, so intervention is necessary to provide the final sealing epidermis. Previously we have shown that Amniotic Membrane (AM) induced a robust...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4540284/ https://www.ncbi.nlm.nih.gov/pubmed/26284363 http://dx.doi.org/10.1371/journal.pone.0135324 |
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author | Alcaraz, Antonia Mrowiec, Anna Insausti, Carmen Luisa Bernabé-García, Ángel García-Vizcaíno, Eva María López-Martínez, María Concepción Monfort, Asunción Izeta, Ander Moraleda, José María Castellanos, Gregorio Nicolás, Francisco José |
author_facet | Alcaraz, Antonia Mrowiec, Anna Insausti, Carmen Luisa Bernabé-García, Ángel García-Vizcaíno, Eva María López-Martínez, María Concepción Monfort, Asunción Izeta, Ander Moraleda, José María Castellanos, Gregorio Nicolás, Francisco José |
author_sort | Alcaraz, Antonia |
collection | PubMed |
description | BACKGROUND: Post-traumatic large-surface or deep wounds often cannot progress to reepithelialisation because they become irresponsive in the inflammatory stage, so intervention is necessary to provide the final sealing epidermis. Previously we have shown that Amniotic Membrane (AM) induced a robust epithelialisation in deep traumatic wounds. METHODS AND FINDINGS: To better understand this phenomenon, we used keratinocytes to investigate the effect of AM on chronic wounds. Using keratinocytes, we saw that AM treatment is able to exert an attenuating effect upon Smad2 and Smad3 TGFß-induced phosphorylation while triggering the activation of several MAPK signalling pathways, including ERK and JNK1, 2. This also has a consequence for TGFß-induced regulation on cell cycle control key players CDK1A (p21) and CDK2B (p15). The study of a wider set of TGFß regulated genes showed that the effect of AM was not wide but very concrete for some genes. TGFß exerted a powerful cell cycle arrest; the presence of AM however prevented TGFß-induced cell cycle arrest. Moreover, AM induced a powerful cell migration response that correlates well with the expression of c-Jun protein at the border of the healing assay. Consistently, the treatment with AM of human chronic wounds induced a robust expression of c-Jun at the wound border. CONCLUSIONS: The effect of AM on the modulation of TGFß responses in keratinocytes that favours proliferation together with AM-induced keratinocyte migration is the perfect match that allows chronic wounds to move on from their non-healing state and progress into epithelialization. Our results may explain why the application of AM on chronic wounds is able to promote epithelialisation. |
format | Online Article Text |
id | pubmed-4540284 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-45402842015-08-24 Amniotic Membrane Modifies the Genetic Program Induced by TGFß, Stimulating Keratinocyte Proliferation and Migration in Chronic Wounds Alcaraz, Antonia Mrowiec, Anna Insausti, Carmen Luisa Bernabé-García, Ángel García-Vizcaíno, Eva María López-Martínez, María Concepción Monfort, Asunción Izeta, Ander Moraleda, José María Castellanos, Gregorio Nicolás, Francisco José PLoS One Research Article BACKGROUND: Post-traumatic large-surface or deep wounds often cannot progress to reepithelialisation because they become irresponsive in the inflammatory stage, so intervention is necessary to provide the final sealing epidermis. Previously we have shown that Amniotic Membrane (AM) induced a robust epithelialisation in deep traumatic wounds. METHODS AND FINDINGS: To better understand this phenomenon, we used keratinocytes to investigate the effect of AM on chronic wounds. Using keratinocytes, we saw that AM treatment is able to exert an attenuating effect upon Smad2 and Smad3 TGFß-induced phosphorylation while triggering the activation of several MAPK signalling pathways, including ERK and JNK1, 2. This also has a consequence for TGFß-induced regulation on cell cycle control key players CDK1A (p21) and CDK2B (p15). The study of a wider set of TGFß regulated genes showed that the effect of AM was not wide but very concrete for some genes. TGFß exerted a powerful cell cycle arrest; the presence of AM however prevented TGFß-induced cell cycle arrest. Moreover, AM induced a powerful cell migration response that correlates well with the expression of c-Jun protein at the border of the healing assay. Consistently, the treatment with AM of human chronic wounds induced a robust expression of c-Jun at the wound border. CONCLUSIONS: The effect of AM on the modulation of TGFß responses in keratinocytes that favours proliferation together with AM-induced keratinocyte migration is the perfect match that allows chronic wounds to move on from their non-healing state and progress into epithelialization. Our results may explain why the application of AM on chronic wounds is able to promote epithelialisation. Public Library of Science 2015-08-18 /pmc/articles/PMC4540284/ /pubmed/26284363 http://dx.doi.org/10.1371/journal.pone.0135324 Text en © 2015 Alcaraz et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Alcaraz, Antonia Mrowiec, Anna Insausti, Carmen Luisa Bernabé-García, Ángel García-Vizcaíno, Eva María López-Martínez, María Concepción Monfort, Asunción Izeta, Ander Moraleda, José María Castellanos, Gregorio Nicolás, Francisco José Amniotic Membrane Modifies the Genetic Program Induced by TGFß, Stimulating Keratinocyte Proliferation and Migration in Chronic Wounds |
title | Amniotic Membrane Modifies the Genetic Program Induced by TGFß, Stimulating Keratinocyte Proliferation and Migration in Chronic Wounds |
title_full | Amniotic Membrane Modifies the Genetic Program Induced by TGFß, Stimulating Keratinocyte Proliferation and Migration in Chronic Wounds |
title_fullStr | Amniotic Membrane Modifies the Genetic Program Induced by TGFß, Stimulating Keratinocyte Proliferation and Migration in Chronic Wounds |
title_full_unstemmed | Amniotic Membrane Modifies the Genetic Program Induced by TGFß, Stimulating Keratinocyte Proliferation and Migration in Chronic Wounds |
title_short | Amniotic Membrane Modifies the Genetic Program Induced by TGFß, Stimulating Keratinocyte Proliferation and Migration in Chronic Wounds |
title_sort | amniotic membrane modifies the genetic program induced by tgfß, stimulating keratinocyte proliferation and migration in chronic wounds |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4540284/ https://www.ncbi.nlm.nih.gov/pubmed/26284363 http://dx.doi.org/10.1371/journal.pone.0135324 |
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