Wound healing involves induction of cyclooxygenase-2 expression in rat skin

Wound healing involves induction of cyclooxygenase-2 expression in rat skin
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DOI:
10.1097/01.lab.0000035024.75914.39
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发表时间:
2002-11-01
影响因子:
5
通讯作者:
Yamanaka, N
Yamanaka, N
中科院分区:
医学2区
文献类型:
--
作者:
Futagami, A;Ishizaki, M;Yamanaka, N

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环氧合酶(考克斯)是前列腺素生物合成所必需的酶,具有两种同工型,考克斯-1和-2。我们研究了大鼠皮肤切除损伤后这两种考克斯蛋白和mRNA的时空变化。我们还定量了这些蛋白质的表达,并研究了特定的考克斯-2抑制剂对愈合的影响。免疫组化和原位杂交结果显示,考克斯-2蛋白和mRNA主要表达于表皮基底层、毛囊外根鞘周围细胞、表皮创缘成纤维样细胞和毛细血管。在正常皮肤中观察到的表达强度远低于损伤皮肤。Western分析显示考克斯-2蛋白在损伤后12小时内开始明显诱导,并在损伤后3天达到峰值。相反,考克斯-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着变化。施用考克斯-2抑制剂延迟了伤口愈合早期的上皮再生,并且还抑制了血管生成。因此,考克斯-2诱导可能是重要的皮肤伤口愈合。
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.