Futagami Ayako, Ishizaki Masamichi, Fukuda Yuh, Kawana Seiji, Yamanaka Nobuaki
Department of Pathology, Nippon Medical School, Tokyo, Japan.
Lab Invest. 2002 Nov;82(11):1503-13. doi: 10.1097/01.lab.0000035024.75914.39.
Cyclooxygenase (COX), an enzyme essential for prostaglandin biosynthesis, has two isoforms, COX-1 and -2. We investigated temporal and spatial changes in localization of these two COX proteins and mRNAs after excisional injury in rat skin. We also quantified the expression of these proteins and studied the effects of a specific COX-2 inhibitor on healing. Immunohistochemistry and in situ hybridization respectively indicated that the COX-2 protein and mRNA were expressed mainly within the basal layer of the epidermis, peripheral cells in the outer root sheath of hair follicles, and fibroblast-like cells and capillaries near epidermal wound edges. Much less intense expression was observed in normal skin than in injured skin. Western analysis demonstrated marked induction of COX-2 protein beginning within 12 hours and peaking 3 days after injury. In contrast, localization of COX-1 protein and mRNA, as well as the amount of protein expression, showed no significant change during wound healing. Administration of the COX-2 inhibitor delayed re-epithelialization in the early phase of wound healing and also inhibited angiogenesis. Thus, COX-2 induction may be important in cutaneous wound healing.
环氧化酶（COX）是前列腺素生物合成所必需的一种酶，有两种同工型，即COX-1和COX-2。我们研究了大鼠皮肤切除损伤后这两种COX蛋白和mRNA定位的时空变化。我们还对这些蛋白的表达进行了定量，并研究了一种特异性COX-2抑制剂对愈合的影响。免疫组织化学和原位杂交分别表明，COX-2蛋白和mRNA主要在表皮基底层、毛囊外根鞘的外周细胞以及表皮伤口边缘附近的成纤维细胞样细胞和毛细血管中表达。正常皮肤中的表达强度远低于损伤皮肤。蛋白质印迹分析表明，COX-2蛋白在损伤后12小时开始显著诱导，并在3天后达到峰值。相比之下，COX-1蛋白和mRNA的定位以及蛋白表达量在伤口愈合过程中没有显著变化。给予COX-2抑制剂会延迟伤口愈合早期的上皮再形成，并且还会抑制血管生成。因此，COX-2的诱导在皮肤伤口愈合中可能很重要。
