Different Expression of μ-Opiate Receptor in Chronic and Acute Wounds and the Effect of β-Endorphin on Transforming Growth Factor β Type II Receptor and Cytokeratin 16 Expression

• Published in: Journal of investigative dermatology Vol. 120; no. 1; pp. 145 - 152
• Main Authors: Bigliardi, P.L., Sumanovski, L.T., Büchner, S., Rufli, T., Bigliardi-Qi, M.
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01.01.2003; Nature Publishing
• Subjects: Acute Disease; beta-Endorphin - pharmacology; Biological and medical sciences; chronic and acute wounds; Chronic Disease; cytokeratin 16; Dermatology; Dose-Response Relationship, Drug; epidermis; Gene Expression Regulation - drug effects; Humans; Investigative techniques, diagnostic techniques (general aspects); Keratins - genetics; Medical sciences; opiate receptor; Organ Culture Techniques; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Protein-Serine-Threonine Kinases; Receptors, Opioid, mu - analysis; Receptors, Transforming Growth Factor beta - genetics; TGF-β receptor II; Wound Healing; Wounds and Injuries - metabolism; β-endorphin; opiate receptor; wound healing; chronic and acute wounds; TGF-β receptor II; β-endorphin; cytokeratin 16; epidermis; Human; Cytokeratin; Transforming growth factor β; Acute; μ Opioid receptor; Tissue culture; Epidermis; β-Endorphin; Neuropeptide; Opioid peptide; Wound; Biological activity; Chronic; Skin; β-endorphin/chronic and acute wounds/cytokeratin 16/epidermis/ ±-opiate receptor/TGF-β receptor II/wound healing; Biological receptor
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1046/j.1523-1747.2003.12018.x

There is evidence that neuropeptides, especially the opiate receptor agonists, are involved in wound healing. We have previously observed that β-endorphin, the endogenous ligand for the μ-opiate receptor, stimulates the expression of cytokeratin 16 in a dose-dependent manner in human skin organ cultures. Cytokeratin 16 is expressed in hyperproliferative epidermis such as psoriasis and wound healing. Therefore we were interested to study whether epidermal μ-opiate receptor expression is changed at the wound margins in acute and chronic wounds. Using classical and confocal microscopy, we were able to compare the expression level of μ-opiate receptors and the influence of β-endorphin on transforming growth factor β type II receptor in organ culture. Our results show indeed a significantly decreased expression of μ-opiate receptors on keratinocytes close to the wound margin of chronic wounds compared to acute wounds. Additionally β-endorphin upregulates the expression of transforming growth factor β type II receptor in human skin organ cultures. These results suggest a crucial role of opioid peptides not only in pain control but also in wound healing. Opioid peptides have already been used in animal models in treatment of wounds; they induce fibroblast proliferation and growth of capillaries, and accelerate the maturation of granulation tissue and the epithelization of the defect. Furthermore opioid peptides may fine-tune pain and the inflammatory response while healing takes place. This new knowledge could potentially be used to design new locally applied drugs to improve the healing of painful chronic wounds.