TY - JOUR
T1 - Deletion of δ-opioid receptor in mice alters skin differentiation and delays wound healing
AU - Bigliardi-Qi, Mei
AU - Gaveriaux-Ruff, Claire
AU - Zhou, Hayan
AU - Hell, Clarisse
AU - Bady, Pierre
AU - Rufli, Theo
AU - Kieffer, Brigitte
AU - Bigliardi, Paul Lorenz
PY - 2006/4
Y1 - 2006/4
N2 - 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.
AB - 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.
KW - Cytokeratin 10
KW - Cytokeratin 6
KW - Delta-opioid receptor
KW - Differentiation
KW - Fibroblasts
KW - Keratinocytes
KW - Knockout mice
KW - Skin
KW - Wound healing
UR - http://www.scopus.com/inward/record.url?scp=33646084156&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646084156&partnerID=8YFLogxK
U2 - 10.1111/j.1432-0436.2006.00065.x
DO - 10.1111/j.1432-0436.2006.00065.x
M3 - Article
C2 - 16683988
AN - SCOPUS:33646084156
VL - 74
SP - 174
EP - 185
JO - Differentiation
JF - Differentiation
SN - 0301-4681
IS - 4
ER -