Stallmeyer Birgit, Anhold Manuel, Wetzler Christian, Kahlina Kornelija, Pfeilschifter Josef, Frank Stefan
Pharmazentrum Frankfurt, Klinikum der Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
Nitric Oxide. 2002 Mar;6(2):168-77. doi: 10.1006/niox.2001.0407.
An important role of inducible nitric oxide (NO) synthase for epithelial action during skin repair has been well established. Although a delayed healing of skin wounds has been recently described for eNOS-deficient mice, a participation of endothelial-type NO synthase (eNOS) in skin repair largely remains unclear. In this study we determined the expression pattern of eNOS during wound healing in healthy and in diabetic mice. Remarkably, normal repair in healthy animals was characterized by a moderate induction of eNOS at the mRNA and protein level, whereas diabetes-impaired healing was associated with a clearly reduced eNOS protein expression. Immunohistochemistry revealed the endothelial lining of blood vessels within the granulation tissue, and also keratinocytes of the wound margins, the developing neo-epithelium, and the hair follicles to express eNOS protein. Keratinocyte-derived expression of eNOS could be confirmed at the mRNA level in vitro for human primary keratinocytes and the keratinocyte cell line HaCaT. Furthermore, eNOS enzymatic activity most likely contributes to epithelial regeneration, as eNOS-deficient (eNOS -/-) animals exhibited reduced wound margin epithelia associated with reduced keratinocyte proliferation.
诱导型一氧化氮（NO）合酶在皮肤修复过程中对上皮作用的重要作用已得到充分证实。尽管最近有人描述内皮型一氧化氮合酶（eNOS）缺陷小鼠的皮肤伤口愈合延迟，但内皮型一氧化氮合酶（eNOS）在皮肤修复中的作用在很大程度上仍不清楚。在本研究中，我们确定了健康小鼠和糖尿病小鼠伤口愈合过程中eNOS的表达模式。值得注意的是，健康动物的正常修复特征是在mRNA和蛋白质水平上适度诱导eNOS，而糖尿病导致的愈合受损与eNOS蛋白表达明显降低有关。免疫组织化学显示，肉芽组织内血管的内皮衬里以及伤口边缘、正在形成的新上皮和毛囊的角质形成细胞均表达eNOS蛋白。在体外，人原代角质形成细胞和角质形成细胞系HaCaT的mRNA水平可证实角质形成细胞来源的eNOS表达。此外，eNOS酶活性很可能有助于上皮再生，因为eNOS缺陷（eNOS-/-）动物的伤口边缘上皮减少，角质形成细胞增殖也减少。
