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Agrin-Matrix Metalloproteinase-12 axis confers a mechanically competent microenvironment in skin wound healing
An orchestrated wound healing program drives skin repair via collective epidermal cell proliferation and migration. However, the molecular determinants of the tissue microenvironment supporting wound healing remain poorly understood. Herein we discover that proteoglycan Agrin is enriched within the...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566503/ https://www.ncbi.nlm.nih.gov/pubmed/34732729 http://dx.doi.org/10.1038/s41467-021-26717-7 |
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author | Chakraborty, Sayan Sampath, Divyaleka Yu Lin, Melissa Ong Bilton, Matthew Huang, Cheng-Kuang Nai, Mui Hoon Njah, Kizito Goy, Pierre-Alexis Wang, Cheng-Chun Guccione, Ernesto Lim, Chwee-Teck Hong, Wanjin |
author_facet | Chakraborty, Sayan Sampath, Divyaleka Yu Lin, Melissa Ong Bilton, Matthew Huang, Cheng-Kuang Nai, Mui Hoon Njah, Kizito Goy, Pierre-Alexis Wang, Cheng-Chun Guccione, Ernesto Lim, Chwee-Teck Hong, Wanjin |
author_sort | Chakraborty, Sayan |
collection | PubMed |
description | An orchestrated wound healing program drives skin repair via collective epidermal cell proliferation and migration. However, the molecular determinants of the tissue microenvironment supporting wound healing remain poorly understood. Herein we discover that proteoglycan Agrin is enriched within the early wound-microenvironment and is indispensable for efficient healing. Agrin enhances the mechanoperception of keratinocytes by augmenting their stiffness, traction stress and fluidic velocity fields in retaliation to bulk substrate rigidity. Importantly, Agrin overhauls cytoskeletal architecture via enhancing actomyosin cables upon sensing geometric stress and force following an injury. Moreover, we identify Matrix Metalloproteinase-12 (MMP12) as a downstream effector of Agrin’s mechanoperception. We also reveal a promising potential of a recombinant Agrin fragment as a bio-additive material that assimilates optimal mechanobiological and pro-angiogenic parameters by engaging MMP12 in accelerated wound healing. Together, we propose that Agrin-MMP12 pathway integrates a broad range of mechanical stimuli to coordinate a competent skin wound healing niche. |
format | Online Article Text |
id | pubmed-8566503 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-85665032021-11-19 Agrin-Matrix Metalloproteinase-12 axis confers a mechanically competent microenvironment in skin wound healing Chakraborty, Sayan Sampath, Divyaleka Yu Lin, Melissa Ong Bilton, Matthew Huang, Cheng-Kuang Nai, Mui Hoon Njah, Kizito Goy, Pierre-Alexis Wang, Cheng-Chun Guccione, Ernesto Lim, Chwee-Teck Hong, Wanjin Nat Commun Article An orchestrated wound healing program drives skin repair via collective epidermal cell proliferation and migration. However, the molecular determinants of the tissue microenvironment supporting wound healing remain poorly understood. Herein we discover that proteoglycan Agrin is enriched within the early wound-microenvironment and is indispensable for efficient healing. Agrin enhances the mechanoperception of keratinocytes by augmenting their stiffness, traction stress and fluidic velocity fields in retaliation to bulk substrate rigidity. Importantly, Agrin overhauls cytoskeletal architecture via enhancing actomyosin cables upon sensing geometric stress and force following an injury. Moreover, we identify Matrix Metalloproteinase-12 (MMP12) as a downstream effector of Agrin’s mechanoperception. We also reveal a promising potential of a recombinant Agrin fragment as a bio-additive material that assimilates optimal mechanobiological and pro-angiogenic parameters by engaging MMP12 in accelerated wound healing. Together, we propose that Agrin-MMP12 pathway integrates a broad range of mechanical stimuli to coordinate a competent skin wound healing niche. Nature Publishing Group UK 2021-11-03 /pmc/articles/PMC8566503/ /pubmed/34732729 http://dx.doi.org/10.1038/s41467-021-26717-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Chakraborty, Sayan Sampath, Divyaleka Yu Lin, Melissa Ong Bilton, Matthew Huang, Cheng-Kuang Nai, Mui Hoon Njah, Kizito Goy, Pierre-Alexis Wang, Cheng-Chun Guccione, Ernesto Lim, Chwee-Teck Hong, Wanjin Agrin-Matrix Metalloproteinase-12 axis confers a mechanically competent microenvironment in skin wound healing |
title | Agrin-Matrix Metalloproteinase-12 axis confers a mechanically competent microenvironment in skin wound healing |
title_full | Agrin-Matrix Metalloproteinase-12 axis confers a mechanically competent microenvironment in skin wound healing |
title_fullStr | Agrin-Matrix Metalloproteinase-12 axis confers a mechanically competent microenvironment in skin wound healing |
title_full_unstemmed | Agrin-Matrix Metalloproteinase-12 axis confers a mechanically competent microenvironment in skin wound healing |
title_short | Agrin-Matrix Metalloproteinase-12 axis confers a mechanically competent microenvironment in skin wound healing |
title_sort | agrin-matrix metalloproteinase-12 axis confers a mechanically competent microenvironment in skin wound healing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566503/ https://www.ncbi.nlm.nih.gov/pubmed/34732729 http://dx.doi.org/10.1038/s41467-021-26717-7 |
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