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Topical application of an irreversible small molecule inhibitor of lysyl oxidases ameliorates skin scarring and fibrosis.
Chaudhari, Nutan; Findlay, Alison D; Stevenson, Andrew W; Clemons, Tristan D; Yao, Yimin; Joshi, Amar; Sayyar, Sepidar; Wallace, Gordon; Rea, Suzanne; Toshniwal, Priyanka; Deng, Zhenjun; Melton, Philip E; Hortin, Nicole; Iyer, K Swaminathan; Jarolimek, Wolfgang; Wood, Fiona M; Fear, Mark W.
Afiliación
  • Chaudhari N; Burn Injury Research Unit, School of Biomedical Sciences, The University of Western Australia, Crawley, Australia.
  • Findlay AD; School of Molecular Sciences, The University of Western Australia, Crawley, Australia.
  • Stevenson AW; Drug Discovery Department, Pharmaxis Ltd, Sydney, NSW, Australia.
  • Clemons TD; Burn Injury Research Unit, School of Biomedical Sciences, The University of Western Australia, Crawley, Australia.
  • Yao Y; School of Molecular Sciences, The University of Western Australia, Crawley, Australia.
  • Joshi A; School of Polymer Science and Engineering, University of Southern Mississippi, Hattiesburg, MS, 39406, USA.
  • Sayyar S; Drug Discovery Department, Pharmaxis Ltd, Sydney, NSW, Australia.
  • Wallace G; Drug Discovery Department, Pharmaxis Ltd, Sydney, NSW, Australia.
  • Rea S; Intelligent Polymer Research Institute, Australian Research Council Centre of Excellence for Electromaterials Science, University of Wollongong, Wollongong, NSW, 2500, Australia.
  • Toshniwal P; Australian National Fabrication Facility-Materials Node, Innovation Campus, University of Wollongong, Wollongong, NSW, 2500, Australia.
  • Deng Z; Intelligent Polymer Research Institute, Australian Research Council Centre of Excellence for Electromaterials Science, University of Wollongong, Wollongong, NSW, 2500, Australia.
  • Melton PE; Australian National Fabrication Facility-Materials Node, Innovation Campus, University of Wollongong, Wollongong, NSW, 2500, Australia.
  • Hortin N; Burns Service of Western Australia, WA, Department of Health, Nedlands, WA, Australia.
  • Iyer KS; Burn Injury Research Unit, School of Biomedical Sciences, The University of Western Australia, Crawley, Australia.
  • Jarolimek W; Burn Injury Research Unit, School of Biomedical Sciences, The University of Western Australia, Crawley, Australia.
  • Wood FM; Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
  • Fear MW; School of Pharmacy and Biomedical Sciences, Curtin University, Bentley, WA, Australia.
Nat Commun ; 13(1): 5555, 2022 09 22.
Article en En | MEDLINE | ID: mdl-36138009
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cicatriz / Proteína-Lisina 6-Oxidasa Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Australia
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cicatriz / Proteína-Lisina 6-Oxidasa Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2022 Tipo del documento: Article País de afiliación: Australia