PUBLICATION
Evidence that xylazine disrupts skin homeostasis by acting on epithelial cells through the kappa opioid receptor
- Authors
- Robertson, T.F., Horn, A., Smith, F.M., Huttenlocher, A.
- ID
- ZDB-PUB-260307-2
- Date
- 2026
- Source
- Disease models & mechanisms 19: dmm052600 (Journal)
- Registered Authors
- Huttenlocher, Anna
- Keywords
- Epidermis, Keratinocytes, Opioid, Wounds, Xylazine
- MeSH Terms
- none
- PubMed
- 41788025 Full text @ Dis. Model. Mech.
Citation
Robertson, T.F., Horn, A., Smith, F.M., Huttenlocher, A. (2026) Evidence that xylazine disrupts skin homeostasis by acting on epithelial cells through the kappa opioid receptor. Disease models & mechanisms. 19:dmm052600.
Abstract
The veterinary sedative and alpha-2 adrenergic receptor (α2AR) agonist xylazine, found in the illicit opioid supply, is associated with cutaneous wounds in humans. Here, we develop a larval zebrafish model of xylazine-induced tissue damage to investigate the mechanisms by which xylazine affects the skin. Xylazine treatment causes keratinocyte extrusion, tissue-wide skin contraction, and the disruption of basal keratinocyte cell-cell interactions in zebrafish larvae. Notably, other α2AR agonists cannot recapitulate most of these effects. Xylazine was recently described as a kappa opioid receptor (κOR) agonist, and we find that both xylazine and a separate κOR agonist can act directly on epithelial cells to drive cellular contraction and disrupt tissue homeostasis. Our model suggests that xylazine may disrupt skin homeostasis through a direct mechanism involving epithelial cells and κOR, which may be of importance for the treatment of these wounds.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping