Hokari Ryota, Kitagawa Noritake, Watanabe Chikako, Komoto Shunsuke, Kurihara Chie, Okada Yoshikiyo, Kawaguchi Atsushi, Nagao Shigeaki, Hibi Toshifumi, Miura Soichiro
Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
J Gastroenterol Hepatol. 2008 Jul;23(7 Pt 2):e88-95. doi: 10.1111/j.1440-1746.2007.05225.x. Epub 2007 Nov 14.
Vascular endothelial growth factor receptor 3 (VEGFR3) and LYVE-1 are specifically expressed in the endothelium of the lymphatic systems. VEGF-C, D, FOXC2, Prox 1, and SOX18 are known to play central roles in lymphatic development. We investigated the expression of regulatory molecules for lymphangiogenesis in the duodenal mucosa of idiopathic intestinal lymphangiectasia.
Biopsy samples were obtained from duodenal biopsies in patients with intestinal lymphangiectasia complicated with protein-losing from white spot lesions in which lymphangiectasia was histologically confirmed. Immunohistochemical analysis for VEGFR3 and LYVE-1 was performed. mRNA expression of VEGF-C, VEGF-D, VEGFR3, and transcription factors was determined by the quantitative reverse transcription-polymerase chain reaction method.
In the control mucosa, VEGFR3 was weakly expressed on the central lymphatic vessels in the lamina propria and LYVE-1 was expressed mainly on the lymphatic vessels in the submucosa. In intestinal lymphangiectasia, VEGFR3 and LYVE-1 expression levels were increased on the mucosal surface corresponding to widely dilated lymphatic vessels, while they were decreased in the deeper mucosa. mRNA expression study showed a significant increase in the expression level of VEGFR3 in lymphangiectasia, but the expression of VEGF-C and -D mRNA was significantly suppressed compared with that in controls despite the presence of lymphangiectasia. The mRNA expression levels of FOXC2 and SOX18 were also decreased, whereas Prox 1 was not altered.
There is an altered expression of regulatory molecules for lymphangiogenesis in the duodenal mucosa in these patients.
血管内皮生长因子受体3（VEGFR3）和淋巴管内皮透明质酸受体1（LYVE-1）在淋巴系统内皮中特异性表达。已知血管内皮生长因子C（VEGF-C）、D（VEGF-D）、叉头框蛋白C2（FOXC2）、Prox1和SRY-盒转录因子18（SOX18）在淋巴管生成中起核心作用。我们研究了特发性肠淋巴管扩张症十二指肠黏膜中淋巴管生成调节分子的表达。
从合并蛋白丢失的肠淋巴管扩张症患者十二指肠活检的白斑病变处获取活检样本，其中淋巴管扩张经组织学证实。对VEGFR3和LYVE-1进行免疫组织化学分析。采用定量逆转录-聚合酶链反应法测定VEGF-C、VEGF-D、VEGFR3和转录因子的mRNA表达。
在对照黏膜中，VEGFR3在固有层中央淋巴管上弱表达，LYVE-1主要在黏膜下层淋巴管上表达。在肠淋巴管扩张症中，对应广泛扩张淋巴管的黏膜表面VEGFR3和LYVE-1表达水平升高，而在更深层黏膜中则降低。mRNA表达研究显示，淋巴管扩张症中VEGFR3表达水平显著升高，但尽管存在淋巴管扩张，VEGF-C和VEGF-D mRNA的表达与对照相比仍显著受抑。FOXC2和SOX18的mRNA表达水平也降低，而Prox1未改变。
这些患者十二指肠黏膜中淋巴管生成调节分子的表达发生了改变。
