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FOXO1 expression in keratinocytes promotes connective tissue healing

Wound healing is complex and highly orchestrated. It is well appreciated that leukocytes, particularly macrophages, are essential for inducing the formation of new connective tissue, which requires the generation of signals that stimulate mesenchymal stem cells (MSC), myofibroblasts and fibroblasts....

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Autores principales: Zhang, Chenying, Lim, Jason, Liu, Jian, Ponugoti, Bhaskar, Alsadun, Sarah, Tian, Chen, Vafa, Rameen, Graves, Dana T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318899/
https://www.ncbi.nlm.nih.gov/pubmed/28220813
http://dx.doi.org/10.1038/srep42834
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author Zhang, Chenying
Lim, Jason
Liu, Jian
Ponugoti, Bhaskar
Alsadun, Sarah
Tian, Chen
Vafa, Rameen
Graves, Dana T.
author_facet Zhang, Chenying
Lim, Jason
Liu, Jian
Ponugoti, Bhaskar
Alsadun, Sarah
Tian, Chen
Vafa, Rameen
Graves, Dana T.
author_sort Zhang, Chenying
collection PubMed
description Wound healing is complex and highly orchestrated. It is well appreciated that leukocytes, particularly macrophages, are essential for inducing the formation of new connective tissue, which requires the generation of signals that stimulate mesenchymal stem cells (MSC), myofibroblasts and fibroblasts. A key role for keratinocytes in this complex process has yet to be established. To this end, we investigated possible involvement of keratinocytes in connective tissue healing. By lineage-specific deletion of the forkhead box-O 1 (FOXO1) transcription factor, we demonstrate for the first time that keratinocytes regulate proliferation of fibroblasts and MSCs, formation of myofibroblasts and production of collagen matrix in wound healing. This stimulation is mediated by a FOXO1 induced TGFβ1/CTGF axis. The results provide direct evidence that epithelial cells play a key role in stimulating connective tissue healing through a FOXO1-dependent mechanism. Thus, FOXO1 and keratinocytes may be an important therapeutic target where healing is deficient or compromised by a fibrotic outcome.
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spelling pubmed-53188992017-02-24 FOXO1 expression in keratinocytes promotes connective tissue healing Zhang, Chenying Lim, Jason Liu, Jian Ponugoti, Bhaskar Alsadun, Sarah Tian, Chen Vafa, Rameen Graves, Dana T. Sci Rep Article Wound healing is complex and highly orchestrated. It is well appreciated that leukocytes, particularly macrophages, are essential for inducing the formation of new connective tissue, which requires the generation of signals that stimulate mesenchymal stem cells (MSC), myofibroblasts and fibroblasts. A key role for keratinocytes in this complex process has yet to be established. To this end, we investigated possible involvement of keratinocytes in connective tissue healing. By lineage-specific deletion of the forkhead box-O 1 (FOXO1) transcription factor, we demonstrate for the first time that keratinocytes regulate proliferation of fibroblasts and MSCs, formation of myofibroblasts and production of collagen matrix in wound healing. This stimulation is mediated by a FOXO1 induced TGFβ1/CTGF axis. The results provide direct evidence that epithelial cells play a key role in stimulating connective tissue healing through a FOXO1-dependent mechanism. Thus, FOXO1 and keratinocytes may be an important therapeutic target where healing is deficient or compromised by a fibrotic outcome. Nature Publishing Group 2017-02-21 /pmc/articles/PMC5318899/ /pubmed/28220813 http://dx.doi.org/10.1038/srep42834 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Zhang, Chenying
Lim, Jason
Liu, Jian
Ponugoti, Bhaskar
Alsadun, Sarah
Tian, Chen
Vafa, Rameen
Graves, Dana T.
FOXO1 expression in keratinocytes promotes connective tissue healing
title FOXO1 expression in keratinocytes promotes connective tissue healing
title_full FOXO1 expression in keratinocytes promotes connective tissue healing
title_fullStr FOXO1 expression in keratinocytes promotes connective tissue healing
title_full_unstemmed FOXO1 expression in keratinocytes promotes connective tissue healing
title_short FOXO1 expression in keratinocytes promotes connective tissue healing
title_sort foxo1 expression in keratinocytes promotes connective tissue healing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318899/
https://www.ncbi.nlm.nih.gov/pubmed/28220813
http://dx.doi.org/10.1038/srep42834
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