Department of Dermatology, Inha Hospital and Inha University School of Medicine, Incheon, South Korea.
Department of Dermatology, Kyungpook National University, Daegu, South Korea.
Exp Dermatol. 2018 Jun;27(6):690-693. doi: 10.1111/exd.13541.
The etiopathogenesis of infantile haemangioma has not been well understood, and it is accepted that angiogenic mediator dysregulation is the main contributor to the abnormal haemangioma capillary formation. The role of NDRG1, a hypoxia-inducible protein; FOXOs, which are tumor suppressor proteins; and the mTOR complex 2 pathway in infantile haemangioma have not been studied yet. The purpose of this study was to investigate NDRG1 and FOXO1 expression in the infantile haemangioma and the correlation of these proteins with proliferation and involution. Primary endothelial cells were obtained, with parental agreement, from 12 infantile haemangioma patients during surgery; 6 patients had proliferating infantile haemangiomas and 6 had involuting IHs. We compared the infantile haemangioma tissues and primary endothelial cells with human vein endothelial cells using microarrays, real-time PCR, Western blotting and immunohistochemical staining. Our data indicated that FOXO1 expression was downregulated in proliferating infantile haemangioma tissue. We found that the expression of NDRG1, a molecule upstream of the FOXO1 pathway, increased during haemangioma proliferation. NDRG1 knockdown decreased haemangioma endothelial cell proliferation and downregulated c-MYC oncoprotein levels. Our findings suggest that NDRG1 positively regulates haemangioma proliferation. FOXO1 dysregulation plays an important role in infantile haemangiomas pathogenesis.
婴儿血管瘤的发病机制尚未完全阐明，人们普遍认为血管生成介质失调是导致异常血管瘤毛细血管形成的主要原因。NDRG1（一种缺氧诱导蛋白）、FOXO（肿瘤抑制蛋白）和 mTOR 复合物 2 通路在婴儿血管瘤中的作用尚未得到研究。本研究旨在探讨 NDRG1 和 FOXO1 在婴儿血管瘤中的表达及其与增殖和消退的相关性。在手术过程中，征得父母同意，从 12 名婴儿血管瘤患者中获得了原代内皮细胞；其中 6 名患者为增殖性婴儿血管瘤，6 名患者为消退性 IHs。我们使用微阵列、实时 PCR、Western blot 和免疫组织化学染色比较了婴儿血管瘤组织和原代内皮细胞与人类静脉内皮细胞的差异。我们的数据表明，FOXO1 表达在增殖性婴儿血管瘤组织中下调。我们发现，FOXO1 通路上游分子 NDRG1 的表达在血管瘤增殖过程中增加。NDRG1 敲低降低了血管瘤内皮细胞的增殖，并下调了 c-MYC 癌蛋白水平。我们的研究结果表明，NDRG1 正向调节血管瘤增殖。FOXO1 失调在婴儿血管瘤发病机制中起重要作用。
