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Combined Metallomics/Transcriptomics Profiling Reveals a Major Role for Metals in Wound Repair

Wilkinson, Holly N.; Guinn, Barbara Ann; Hardman, Matthew J.



Endogenous metals are required for all life, orchestrating the action of diverse cellular processes that are crucial for tissue function. The dynamic wound healing response is underpinned by a plethora of such cellular behaviours, occurring in a time-dependent manner. However, the importance of endogenous metals for cutaneous repair remains largely unexplored. Here we combine ICP-MS with tissue-level RNA-sequencing to reveal profound changes in a number of metals, and corresponding metal-regulated genes, across temporal healing in mice. Wound calcium, magnesium, iron, copper and manganese are elevated at 7 days post-wounding, while magnesium, iron, aluminium, manganese and cobalt increase at 14 days post-wounding. At the level of transcription, wound-induced pathways are independently highly enriched for metal-regulated genes, and vice versa. Moreover, specific metals are linked to distinct wound-induced biological processes and converge on key transcriptional regulators in mice and humans. Finally, we reveal a potential role for one newly identified transcriptional regulator, TNF, in calcium-induced epidermal differentiation. Together, these data highlight potential new and diverse roles for metals in cutaneous wound repair, paving the way for further studies to elucidate the contribution of metals to cellular processes in the repair of skin and other tissues.


Wilkinson, H. N., Guinn, B. A., & Hardman, M. J. (2021). Combined Metallomics/Transcriptomics Profiling Reveals a Major Role for Metals in Wound Repair. Frontiers in Cell and Developmental Biology, 9, Article 788596.

Journal Article Type Article
Acceptance Date Nov 11, 2021
Online Publication Date Nov 30, 2021
Publication Date Nov 30, 2021
Deposit Date Dec 16, 2021
Publicly Available Date Dec 17, 2021
Journal Frontiers in Cell and Developmental Biology
Electronic ISSN 2296-634X
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 9
Article Number 788596
Keywords Metallome; Wound healing; Skin; RNA-sequencing; Calcium; Metals
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Copyright Statement
Copyright © 2021 Wilkinson, Guinn and Hardman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice.No use, distribution or reproduction is permitted which does not comply with these terms.

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