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Changes in regulatory molecules for lymphangiogenesis in intestinal lymphangiectasia with enteric protein loss
Abstract
Background and Aim: 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.
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In protein-losing enteropathy, serum albumin concentration decreases, vascular permeability increases, absolute synthesis increases, half-life decreases, total mass decreases, distribution volume increases, and VEGF increases.
“Protein‐losing enteropathy | ↓ to ↓↓↓ | ↑ to↑↑↑ | ↑ to↑↑↑ | ↓ to ↓↓ | ↓ to ↓↓↓ | ↑ to↑↑↑ | ↑43 | Albumin mass↓ due to protein loss and shortened half‐life”
From Hypoalbuminemia: Pathogenesis and Clinical Significance (2019) · cites this paper as [43]
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Hypoalbuminemia: Pathogenesis and Clinical Significance
Soeters, P. B., Wolfe, R. R., & Shenkin, A. (2019) · Journal of Parenteral and Enteral Nutrition · doi:10.1002/jpen.1451 · Cited by 1,448
Metadata
- Authors
- Hokari, R., Kitagawa, N., Watanabe, C., Komoto, S., Kurihara, C., Okada, Y., Kawaguchi, A., Nagao, S., Hibi, T., & Miura, S.
- Affiliations
- National Defense Medical College (JP)
- Corresponding author
- Hokari, Ryota
- Venue
- Journal of Gastroenterology and Hepatology
- Publisher
- Wiley
- Published
- 2008-07
- Volume
- 23
- Issue
- 7pt2
- Pages
- e88-95
- ISSN
- 0815-9319 (ISSN-L)
- 1440-1746
- OpenAlex
- W1991331872
- Cited by
- 70
- References
- 0
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2023: 5 · 2022: 6 · 2021: 5 · 2020: 3 · 2019: 3 · 2018: 1 · 2017: 5 · 2016: 4 · 2015: 5 · 2014: 5 · 2013: 1 · 2012: 4
- FWCI
- 1.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Gastroenterology and Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Lymphatic System and Diseases
- Health Sciences › Medicine › Surgery › Lymphatic Disorders and Treatments
- Health Sciences › Medicine › Surgery › Vascular Malformations and Hemangiomas
- Keywords
- intestinal lymphangiectasia, lymphangiogenesis, VEGFR-3, LYVE-1, VEGF-C, VEGF-D, FOXC2, SOX18, Prox1, protein-losing enteropathy, duodenal mucosa, lymphatic endothelium, gene expression
- MeSH terms
- Prospero-Related Homeobox 1 Protein, Adult, Aged, Duodenoscopy, Duodenum, Endothelium, Lymphatic, Female, High Mobility Group Proteins, Humans, Immunohistochemistry, Intestinal Mucosa, Lymphangiectasis, Intestinal, Male, Middle Aged, Protein-Losing Enteropathies, RNA, Messenger, Transcription Factors, Case-Control Studies, Homeodomain Proteins, Reverse Transcriptase Polymerase Chain Reaction, Tumor Suppressor Proteins, Vesicular Transport Proteins, Vascular Endothelial Growth Factor Receptor-3, Vascular Endothelial Growth Factor C, Lymphangiogenesis, Vascular Endothelial Growth Factor D, Intracellular Signaling Peptides and Proteins, Forkhead Transcription Factors, SOXF Transcription Factors
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