Changes in regulatory molecules for lymphangiogenesis in intestinal lymphangiectasia with enteric protein loss

Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
Journal of Gastroenterology and Hepatology (Impact Factor: 3.5). 12/2007; 23(7 Pt 2):e88-95. DOI: 10.1111/j.1440-1746.2007.05225.x
Source: PubMed


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.

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    • "It is congenital or idiopathic, and has been linked to several syndromes including Milroy's, Von Recklinghausen, Turner, Klippel Trenaunay, Hennekam, and Noonan's (Keberle et al. 2000; Suresh et al. 2009). An immunohistochemical study by Hokari et al. (2008) identified several growth factors and receptors significant in lymphangiogenesis and lymphangiectasia, namely VEGF-C and -D, FOXC2, SOX18, Prox 1, and VEGFR3 and LYVE-1, respectively, the latter two of which were specific and sensitive markers for lymphatics. Macdonald et al. (2010) recently found an association between PIL and severity of small intestinal angiodysplasia. "
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    • "sia is characterized by highly dilated lymphatic capil - laries in the intestinal villi . Because the normal lymphatic response to changes in interstitial pressure is hindered by this hyperdilation , absorption by the intestine is compro - mised . Moreover , the levels of FOXC2 and SOX18 tran - scription are significantly lower in these patients ( Hokari et al . 2008 ; Johnson and Oliver 2009 ) ."
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    • "Several genes, such as VEGFR3 (vascular endothelial growth factor receptor 3), prospero-related homeobox-transcriptional factor PROX1, forkhead transcriptional factor FOXC2 and SOX18 are implicated in the development of the lymphatic system. In a recent paper, Hokari et al. reported inconsistently changed expressions of regulatory molecules for lymphangiogenesis in the duodenal mucosa of PIL patients [24]. "
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