LymphedemaV1, PubMed, Corpus, bibRecord, 000B92

VEGF-C is required for intestinal lymphatic vessel maintenance and lipid absorption.

Identifieur interne : 000B92 ( PubMed/Corpus ); précédent : 000B91; suivant : 000B93

VEGF-C is required for intestinal lymphatic vessel maintenance and lipid absorption.

Auteurs : Harri Nurmi ; Pipsa Saharinen ; Georgia Zarkada ; Wei Zheng ; Marius R. Robciuc ; Kari Alitalo

Source :

EMBO molecular medicine [ 1757-4684 ] ; 2015.

RBID : pubmed:26459520

English descriptors

KwdEn :
- Animals, Gene Deletion, Intestines (physiology), Lipid Metabolism, Lymphatic Vessels (physiology), Mice, Mice, Knockout, Vascular Endothelial Growth Factor C (genetics), Vascular Endothelial Growth Factor C (metabolism).
MESH :
- chemical , genetics : Vascular Endothelial Growth Factor C.
- chemical , metabolism : Vascular Endothelial Growth Factor C.
- physiology : Intestines, Lymphatic Vessels.
- Animals, Gene Deletion, Lipid Metabolism, Mice, Mice, Knockout.

Abstract

Vascular endothelial growth factor C (VEGF-C) binding to its tyrosine kinase receptor VEGFR-3 drives lymphatic vessel growth during development and in pathological processes. Although the VEGF-C/VEGFR-3 pathway provides a target for treatment of cancer and lymphedema, the physiological functions of VEGF-C in adult vasculature are unknown. We show here that VEGF-C is necessary for perinatal lymphangiogenesis, but required for adult lymphatic vessel maintenance only in the intestine. Following Vegfc gene deletion in adult mice, the intestinal lymphatic vessels, including the lacteal vessels, underwent gradual atrophy, which was aggravated when also Vegfd was deleted. VEGF-C was expressed by a subset of smooth muscle cells adjacent to the lacteals in the villus and in the intestinal wall. The Vegfc-deleted mice showed defective lipid absorption and increased fecal excretion of dietary cholesterol and fatty acids. When fed a high-fat diet, the Vegfc-deficient mice were resistant to obesity and had improved glucose metabolism. Our findings indicate that the lymphangiogenic growth factors provide trophic and dynamic regulation of the intestinal lymphatic vasculature, which could be especially important in the dietary regulation of adiposity and cholesterol metabolism.

DOI: 10.15252/emmm.201505731
PubMed: 26459520

Links to Exploration step

pubmed:26459520

Le document en format XML

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<author><name sortKey="Saharinen, Pipsa" sort="Saharinen, Pipsa" uniqKey="Saharinen P" first="Pipsa" last="Saharinen">Pipsa Saharinen</name>
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<author><name sortKey="Zarkada, Georgia" sort="Zarkada, Georgia" uniqKey="Zarkada G" first="Georgia" last="Zarkada">Georgia Zarkada</name>
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<author><name sortKey="Zheng, Wei" sort="Zheng, Wei" uniqKey="Zheng W" first="Wei" last="Zheng">Wei Zheng</name>
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<author><name sortKey="Robciuc, Marius R" sort="Robciuc, Marius R" uniqKey="Robciuc M" first="Marius R" last="Robciuc">Marius R. Robciuc</name>
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<author><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name>
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<author><name sortKey="Zarkada, Georgia" sort="Zarkada, Georgia" uniqKey="Zarkada G" first="Georgia" last="Zarkada">Georgia Zarkada</name>
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<author><name sortKey="Zheng, Wei" sort="Zheng, Wei" uniqKey="Zheng W" first="Wei" last="Zheng">Wei Zheng</name>
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<term>Lymphatic Vessels (physiology)</term>
<term>Mice</term>
<term>Mice, Knockout</term>
<term>Vascular Endothelial Growth Factor C (genetics)</term>
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<front><div type="abstract" xml:lang="en">Vascular endothelial growth factor C (VEGF-C) binding to its tyrosine kinase receptor VEGFR-3 drives lymphatic vessel growth during development and in pathological processes. Although the VEGF-C/VEGFR-3 pathway provides a target for treatment of cancer and lymphedema, the physiological functions of VEGF-C in adult vasculature are unknown. We show here that VEGF-C is necessary for perinatal lymphangiogenesis, but required for adult lymphatic vessel maintenance only in the intestine. Following Vegfc gene deletion in adult mice, the intestinal lymphatic vessels, including the lacteal vessels, underwent gradual atrophy, which was aggravated when also Vegfd was deleted. VEGF-C was expressed by a subset of smooth muscle cells adjacent to the lacteals in the villus and in the intestinal wall. The Vegfc-deleted mice showed defective lipid absorption and increased fecal excretion of dietary cholesterol and fatty acids. When fed a high-fat diet, the Vegfc-deficient mice were resistant to obesity and had improved glucose metabolism. Our findings indicate that the lymphangiogenic growth factors provide trophic and dynamic regulation of the intestinal lymphatic vasculature, which could be especially important in the dietary regulation of adiposity and cholesterol metabolism.</div>
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<Abstract><AbstractText>Vascular endothelial growth factor C (VEGF-C) binding to its tyrosine kinase receptor VEGFR-3 drives lymphatic vessel growth during development and in pathological processes. Although the VEGF-C/VEGFR-3 pathway provides a target for treatment of cancer and lymphedema, the physiological functions of VEGF-C in adult vasculature are unknown. We show here that VEGF-C is necessary for perinatal lymphangiogenesis, but required for adult lymphatic vessel maintenance only in the intestine. Following Vegfc gene deletion in adult mice, the intestinal lymphatic vessels, including the lacteal vessels, underwent gradual atrophy, which was aggravated when also Vegfd was deleted. VEGF-C was expressed by a subset of smooth muscle cells adjacent to the lacteals in the villus and in the intestinal wall. The Vegfc-deleted mice showed defective lipid absorption and increased fecal excretion of dietary cholesterol and fatty acids. When fed a high-fat diet, the Vegfc-deficient mice were resistant to obesity and had improved glucose metabolism. Our findings indicate that the lymphangiogenic growth factors provide trophic and dynamic regulation of the intestinal lymphatic vasculature, which could be especially important in the dietary regulation of adiposity and cholesterol metabolism.</AbstractText>
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VEGF-C is required for intestinal lymphatic vessel maintenance and lipid absorption.

VEGF-C is required for intestinal lymphatic vessel maintenance and lipid absorption.

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