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
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
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DOI：
10.1046/j.1523-1747.2003.12018.x
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发表时间：
2003-01-01
影响因子：
6.5
通讯作者：
Bigliardi-Qi, M
中科院分区：
文献类型：
--
作者：
Bigliardi, PL;Sumanovski, LT;Bigliardi-Qi, M
有证据表明，神经肽，特别是阿片受体激动剂，参与伤口愈合。我们先前已经观察到，β-内啡肽，μ-阿片受体的内源性配体，刺激细胞角蛋白16的表达在人皮肤器官培养物中以剂量依赖性方式。细胞角蛋白16在过度增殖的表皮如银屑病和伤口愈合中表达。因此，我们有兴趣研究表皮μ阿片受体表达是否在急性和慢性伤口的伤口边缘改变。使用经典和共聚焦显微镜，我们能够比较μ-阿片受体的表达水平和β-内啡肽对转化生长因子β II型受体在器官培养的影响。我们的研究结果表明，与急性伤口相比，慢性伤口的伤口边缘附近的角质形成细胞上μ阿片受体的表达确实显著降低。此外，β-内啡肽上调人皮肤器官培养物中转化生长因子β II型受体的表达。这些结果表明阿片肽不仅在疼痛控制方面而且在伤口愈合方面都发挥着至关重要的作用。阿片肽已经用于治疗伤口的动物模型中;它们诱导成纤维细胞增殖和毛细血管生长，并加速肉芽组织的成熟和缺损的上皮化。此外，阿片肽可以在愈合发生时微调疼痛和炎症反应。这一新知识可能被用于设计新的局部应用药物，以改善疼痛的慢性伤口的愈合。
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.