Please use this identifier to cite or link to this item: https://doi.org/10.1038/s41467-021-26717-7
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dc.titleAgrin-Matrix Metalloproteinase-12 axis confers a mechanically competent microenvironment in skin wound healing
dc.contributor.authorChakraborty, Sayan
dc.contributor.authorSampath, Divyaleka
dc.contributor.authorYu Lin, Melissa Ong
dc.contributor.authorBilton, Matthew
dc.contributor.authorHuang, Cheng-Kuang
dc.contributor.authorNai, Mui Hoon
dc.contributor.authorNjah, Kizito
dc.contributor.authorGoy, Pierre-Alexis
dc.contributor.authorWang, Cheng-Chun
dc.contributor.authorGuccione, Ernesto
dc.contributor.authorLim, Chwee-Teck
dc.contributor.authorHong, Wanjin
dc.date.accessioned2022-10-12T07:54:03Z
dc.date.available2022-10-12T07:54:03Z
dc.date.issued2021-11-03
dc.identifier.citationChakraborty, 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 (2021-11-03). Agrin-Matrix Metalloproteinase-12 axis confers a mechanically competent microenvironment in skin wound healing. Nature Communications 12 (1) : 6349. ScholarBank@NUS Repository. https://doi.org/10.1038/s41467-021-26717-7
dc.identifier.issn2041-1723
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/232287
dc.description.abstractAn 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. © 2021, The Author(s).
dc.publisherNature Research
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceScopus OA2021
dc.typeArticle
dc.contributor.departmentMECHANOBIOLOGY INSTITUTE
dc.contributor.departmentCOLLEGE OF DESIGN AND ENGINEERING
dc.contributor.departmentINST FOR HEALTH INNOVATION & TECHNOLOGY
dc.description.doi10.1038/s41467-021-26717-7
dc.description.sourcetitleNature Communications
dc.description.volume12
dc.description.issue1
dc.description.page6349
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