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Targeting Cx26 Expression by Sustained Release of Cx26 Antisense from Scaffolds Reduces Inflammation and Improves Wound Healing

Phillips, ARJ; Chin, JS; Madden, L; Gilmartin, DJ; Soon, A; Thrasivoulou, C; Jayasinghe, SN; ... Becker, DL; + view all (2018) Targeting Cx26 Expression by Sustained Release of Cx26 Antisense from Scaffolds Reduces Inflammation and Improves Wound Healing. Advanced Biosystems , 2 (12) , Article 1800227. 10.1002/adbi.201800227. Green open access

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Abstract

The gap junction protein connexin 26 (Cx26) is expressed at high levels in naturally hyperthickened epidermal layers as well as pathological hyperkeratotic disease states, such as warts, psoriatic plaques, and chronic wound edges. The overexpression of Cx26 is also linked with inflammation, breakdown of the skin barrier function, and perturbed wound healing. Here, a collagen scaffold implanted into a rat excisional skin wound is used. This induces a foreign body type reaction characterized by epidermal thickening with elevated levels of Cx43 and Cx26, increased inflammation, and perturbed healing. This is reminiscent of a chronic skin wound. If the same scaffolds are coated with an antisense molecule specifically targeting Cx26 that has a slow sustained release, this prevents the abnormal upregulation of Cx26 protein at the wound edge. Knocking down Cx26 protein levels below those seen in normal wound healing has no adverse effects on the healing process but instead reduces the epidermal thickening and also the inflammatory response, while at the same time promotes the healing response. Treatment with Cx43/26 antisense may promote healing of chronic wounds. The Cx26 antisense may also be helpful in treating other skin conditions where Cx26 is overexpressed.

Type: Article
Title: Targeting Cx26 Expression by Sustained Release of Cx26 Antisense from Scaffolds Reduces Inflammation and Improves Wound Healing
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/adbi.201800227
Publisher version: https://doi.org/10.1002/adbi.201800227
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: antisense delivery, Cx26, scaffold, tissue repair
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10089407
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