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Reduced iron in diabetic wounds: An oxidative stress-dependent role for STEAP3 in extracellular matrix deposition and remodelling

Wilkinson, Holly N.; Upson, Sophie E.; Banyard, Kayleigh L.; Knight, Robert; Mace, Kimberly A.; Hardman, Matthew J.

Authors

Holly N. Wilkinson

Sophie E. Upson

Kayleigh L. Banyard

Robert Knight

Kimberly A. Mace

Matthew J. Hardman



Abstract

Iron is crucial for maintaining normal bodily function, with well-documented roles in erythropoiesis, haemostasis and inflammation. Despite this, little is known about the temporal regulation of iron during wound healing, nor how iron contributes to wound biology and pathology. Here we profiled tissue iron levels across a healing time-course, identifying iron accumulation during late-stage repair. Interestingly, diabetic murine wounds displayed significantly reduced iron levels, delayed extracellular matrix deposition and dysregulation of iron gene expression. In vitro studies revealed important cellular roles for iron, promoting both deposition and remodelling of extracellular proteins. Functional studies identified oxidative stress-dependent upregulation of the iron-converting metalloreductase, STEAP3, as a key mediator of extracellular matrix production. Taken together, these data reveal a to our knowledge previously unreported mechanistic role for iron in facilitating the remodelling stage of wound healing. Indeed, targeting tissue iron may be a promising future strategy to tackle the development and progression of chronic wounds.

Journal Article Type Article
Publication Date 2019-11
Journal Journal of Investigative Dermatology
Print ISSN 0022-202x
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 139
Issue 11
Pages 2368-2377.e7
APA6 Citation Wilkinson, H. N., Upson, S. E., Banyard, K. L., Knight, R., Mace, K. A., & Hardman, M. J. (2019). Reduced iron in diabetic wounds: An oxidative stress-dependent role for STEAP3 in extracellular matrix deposition and remodelling. Journal of Investigative Dermatology, 139(11), 2368-2377.e7. https://doi.org/10.1016/j.jid.2019.05.014
DOI https://doi.org/10.1016/j.jid.2019.05.014
Keywords Cell Biology; Biochemistry; Molecular Biology; Dermatology
Publisher URL https://www.sciencedirect.com/science/article/pii/S0022202X19316331

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.





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