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Topical application of an irreversible small molecule inhibitor of lysyl oxidases ameliorates skin scarring and fibrosis
Citation
Chaudhari, N and Findlay, AD and Stevenson, AW and Clemons, TD and Yao, Y and Joshi, A and Sayyar, S and Wallace, G and Rea, S and Toshniwal, P and Deng, Z and Melton, PE and Hortin, N and Iyer, KS and Jarolimek, W and Wood, FM and Fear, MW, Topical application of an irreversible small molecule inhibitor of lysyl oxidases ameliorates skin scarring and fibrosis, Nature Communications, 13, (1) pp. 1-14. ISSN 2041-1723 (2022) [Refereed Article]
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DOI: doi:10.1038/s41467-022-33148-5
Abstract
Scarring is a lifelong consequence of skin injury, with scar stiffness and poor
appearance presenting physical and psychological barriers to a return to
normal life. Lysyl oxidases are a family of enzymes that play a critical role in
scar formation and maintenance. Lysyl oxidases stabilize the main component
of scar tissue, collagen, and drive scar stiffness and appearance. Here we
describe the development and characterisation of an irreversible lysyl oxidase
inhibitor, PXS-6302. PXS-6302 is ideally suited for skin treatment, readily
penetrating the skin when applied as a cream and abolishing lysyl oxidase
activity. In murine models of injury and fibrosis, topical application reduces
collagen deposition and cross-linking. Topical application of PXS-6302 after
injury also significantly improves scar appearance without reducing tissue
strength in porcine injury models. PXS-6302 therefore represents a promising
therapeutic to ameliorate scar formation, with potentially broader applications in other fibrotic diseases.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | scars, wound healing, DNA methylation, RNA-Seq, fibrosis |
| Research Division: | Biological Sciences |
| Research Group: | Bioinformatics and computational biology |
| Research Field: | Genomics and transcriptomics |
| Objective Division: | Health |
| Objective Group: | Clinical health |
| Objective Field: | Clinical health not elsewhere classified |
| UTAS Author: | Melton, PE (Dr Phillip Melton) |
| ID Code: | 155442 |
| Year Published: | 2022 |
| Web of Science® Times Cited: | 2 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2023-02-20 |
| Last Modified: | 2023-02-21 |
| Downloads: | 0 |
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