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

Abstract

There is evidence that neuropeptides, especially the opiate receptor agonists, are involved in wound healing. We have previously observed that beta-endorphin, the endogenous ligand for the mu-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 mu-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 mu-opiate receptors and the influence of beta-endorphin on transforming growth factor beta type II receptor in organ culture. Our results show indeed a significantly decreased expression of mu-opiate receptors on keratinocytes close to the wound margin of chronic wounds compared to acute wounds. Additionally beta-endorphin upregulates the expression of transforming growth factor beta 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.

The Preventive Effect of Coffee Compounds on Dermatitis and Epidermal Pigmentation after Ultraviolet Irradiation in Mice

“…β-Endorphin has been reported to exert an anti-inflammatory effect on the skin [38] and to participate in the inhibitory action of UVB-induced melanocyte activation [39]. A previous study found that α-MSH and β-endorphin have opposing biological activities, with α-MSH stimulating adenylate cyclase inducing an increase in cAMP while β-endorphin decreases this α-MSH-generated cAMP accumulation [40].…”

Endocrine controls of keratin expression

“…Wound healing (98) Prolactin K8 " Knockout mice lacking the PRL receptor showed decreased expression of keratins K8, K17, K18, and K19 during early pregnancy, accompanied by failure to develop normal mammary glands.…”

Opioids As Modulators of Cell Death and Survival—Unraveling Mechanisms and Revealing New Indications

“…However, the dose of 2 to 8 mg/kg is in the range of effective antinociceptive doses for rats and therefore probably was too high to facilitate angiogenesis. The endogenous MOR and DOR agonist ␤-endorphin was reported to stimulate the expression of cytokeratin 16 (Bigliardi-Qi et al, 2000) and transforming growth factor ␤ type II (Bigliardi et al, 2003) in human skin organ cultures. Both, CK16 and TGF␤ type II receptor are not expressed in normal skin but appear in regenerating epithelial cells of the epidermis during wound healing.…”