Identification of Signaling Systems in Proliferating and Involuting Phase Infantile Hemangiomas by Genome-Wide Transcriptional Profiling
Identification of Signaling Systems in Proliferating and Involuting Phase Infantile Hemangiomas by Genome-Wide Transcriptional Profiling
复制标题
DOI：
10.2353/ajpath.2009.080517
复制
发表时间：
2009-05-01
影响因子：
6
通讯作者：
Kozakewich, Harry P.
中科院分区：
文献类型：
--
作者：
Calicchio, Monica L.;Collins, Tucker;Kozakewich, Harry P.
婴儿血管瘤的特征是在生命的第一年毛细血管快速生长，然后在儿童早期消退。这些病变的自然历史为研究这些肿瘤增殖和退化时血管中基因表达的变化创造了独特的机会。在这里，我们使用激光捕获显微解剖和全基因组转录图谱的血管增殖期和消退期，以确定差异表达的基因。与正常胎盘血管相比，增生性血管瘤的特征是参与内皮-周细胞相互作用的基因表达增加，如血管生成素-2(ANGPT2)、锯齿状-1(JAG1)和缺口-4(NOTCH4)，以及参与神经和血管构型的基因，如神经粘连蛋白-2(Neto2)、含丛蛋白结构域的受体(PlexinC1)和肾上腺素受体(EPHB3)。胰岛素样生长因子结合蛋白-3(IGFBP3)在增生性血管瘤中表达下调。消退期血管瘤的特征是表达慢性炎症介质，如趋化因子、基质细胞衍生因子-1(SDF-1)，以及可能减弱血管生成反应的因子，如唐氏综合征关键区(DSCR)家族的成员。在活体内识别在增生性和消退性血管瘤中差异表达的基因将有助于我们理解这种血管病变，它仍然是新生儿发病率的主要原因。(Am J Pathol 2009174：1638-1649；doi：10.2353/ajpath.2009.080517)
Infantile hemangiomas are characterized by rapid capillary growth during the first year of life followed by involution during early childhood. The natural history of these lesions creates a unique opportunity to study the changes in gene expression that occur in the vessels of these tumors as they proliferate and regress. Here we use laser capture microdissection and genome-wide transcriptional profiling of vessels from proliferating and involuting hemangiomas to identify differentially expressed genes. Relative to normal placental vessels, proliferating hemangiomas were characterized by increased expression of genes involved in endothelial-pericyte interactions, such as angiopoietin-2 (ANGPT2), jagged-1 (JAG1), and notch-4 (NOTCH4), as well as genes involved in neural and vascular patterning, such as neuropilin-2 (NETO2), a plexin domain containing receptor (plexinC1), and an ephrin receptor (EPHB3). Insulin-like growth factor binding protein-3 (IGFBP3) was down-regulated in proliferating hemangiomas. Involuting hemangiomas were characterized by the expression of chronic inflammatory mediators, such as the chemokine, stromal cell-derived factor-1 (SDF-1), and factors that may attenuate the angiogenic response, such as a member of the Down syndrome critical region (DSCR) family. The identification of genes differentially expressed in proliferating and involuting hemangiomas in vivo will contribute to our understanding of this vascular lesion, which remains a leading cause of morbidity in newborn children. (Am J Pathol 2009, 174:16 38-1649; DOI: 10.2353/ajpath.2009.080517)