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


METHODS
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.


RESULTS
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.


CONCLUSIONS
There is an altered expression of regulatory molecules for lymphangiogenesis in the duodenal mucosa in these patients.
Hokari
Ryota
R
Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
Kitagawa
Noritake
N
Watanabe
Chikako
C
Komoto
Shunsuke
S
Kurihara
Chie
C
Okada
Yoshikiyo
Y
Kawaguchi
Atsushi
A
Nagao
Shigeaki
S
Hibi
Toshifumi
T
Miura
Soichiro
S
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004384:Duodenoscopy; D004386:Duodenum / Q000737:chemistry* / Q000473:pathology / Q000503:physiopathology; D004729:Endothelium, Lymphatic / Q000737:chemistry* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D006609:High Mobility Group Proteins / Q000032:analysis; D018398:Homeodomain Proteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000737:chemistry* / Q000473:pathology / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis* / Q000235:genetics; D008201:Lymphangiectasis, Intestinal / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D042583:Lymphangiogenesis; D008297:Male; D008875:Middle Aged; D011504:Protein-Losing Enteropathies / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055760:SOXF Transcription Factors; D014157:Transcription Factors / Q000032:analysis* / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000032:analysis; D042582:Vascular Endothelial Growth Factor C / Q000032:analysis; D042643:Vascular Endothelial Growth Factor D / Q000032:analysis; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000032:analysis; D033921:Vesicular Transport Proteins / Q000032:analysis; D000098551:Prospero-Related Homeobox 1 Protein
D051858:Forkhead Transcription Factors; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; C119248:LYVE1 protein, human; D012333:RNA, Messenger; C095473:SOX18 protein, human; D055760:SOXF Transcription Factors; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D033921:Vesicular Transport Proteins; C082078:mesenchyme fork head 1 protein; D000098551:Prospero-Related Homeobox 1 Protein; D040321:Vascular Endothelial Growth Factor Receptor-3