Deletion of δ-opioid receptor in mice alters skin differentiation and delays wound healing

Mei Bigliardi-Qi, Claire Gaveriaux-Ruff, Hayan Zhou, Clarisse Hell, Pierre Bady, Theo Rufli, Brigitte Kieffer, Paul Lorenz Bigliardi

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


In addition to their well-known antinociceptive action, opioids can modulate non-neuronal functions, such as immune activity and physiology of different cell types. Several findings suggest that the δ-opioid receptor (DOR) and its endogenous ligands (enkephalins) are important players in cell differentiation and proliferation. Here we show the expression of DOR in mouse skin and human skin cultured fibroblasts and keratinocytes using RT-PCR. In DOR knock-out (KO) mice, a phenotype of thinner epidermis and higher expression of cell differentiation marker cytokeratin 10 (CK 10) were observed compared with wild type (WT). Using a burn wound model, significant wound healing delay (about 2 days) and severe epidermal hypertrophy were shown at the wound margin of DOR KO mice. This wound healing delay was further investigated by immunohistochemistry using markers for proliferation, differentiation, re-epithelialization, and dermal repair (CK 6, CK 10, and collagen IV). The levels of all these markers were increased in wounds of KO mice compared with WT. During the wound healing, the epidermal thickness in KO mice augments faster and exceeds that of the WT by day 3. These results suggest an essential role of DOR in skin differentiation, proliferation, and migration, factors that are important for wound healing.

Original languageEnglish (US)
Pages (from-to)174-185
Number of pages12
Issue number4
StatePublished - Apr 2006

Bibliographical note

Funding Information:
B. Ilmer and A. Reijs are supported by the Dutch Heart Foundation (grant NHS 87.079). M Pozzoli is supported by Fondazione dinka del Lavoro, Centro Medico di Montescano, Pavia, Italy. A. Salustri is supported by the Interuniversity Cardiology Institute of The Netherlands (grant no. 5442).


  • Cytokeratin 10
  • Cytokeratin 6
  • Delta-opioid receptor
  • Differentiation
  • Fibroblasts
  • Keratinocytes
  • Knockout mice
  • Skin
  • Wound healing


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