An unexpected role of semaphorin3a-neuropilin-1 signaling in lymphatic vessel maturation and valve formation.

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State: Serval
Version: author
Serval ID
serval:BIB_3F58C69BAE88
Type
Article: article from journal or magazin.
Collection
Publications
Title
An unexpected role of semaphorin3a-neuropilin-1 signaling in lymphatic vessel maturation and valve formation.
Journal
Circulation Research
Author(s)
Jurisic G., Maby-El Hajjami H., Karaman S., Ochsenbein A.M., Alitalo A., Siddiqui S.S., Ochoa Pereira C., Petrova T.V., Detmar M.
ISSN
1524-4571 (Electronic)
ISSN-L
0009-7330
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
111
Number
4
Pages
426-436
Language
english
Abstract
RATIONALE: Lymphatic vasculature plays important roles in tissue fluid homeostasis maintenance and in the pathology of human diseases. Yet, the molecular mechanisms that control lymphatic vessel maturation remain largely unknown.
OBJECTIVE: We analyzed the gene expression profiles of ex vivo isolated lymphatic endothelial cells to identify novel lymphatic vessel expressed genes and we investigated the role of semaphorin 3A (Sema3A) and neuropilin-1 (Nrp-1) in lymphatic vessel maturation and function.
METHODS AND RESULTS: Lymphatic and blood vascular endothelial cells from mouse intestine were isolated using fluorescence-activated cell sorting, and transcriptional profiling was performed. We found that the axonal guidance molecules Sema3A and Sema3D were highly expressed by lymphatic vessels. Importantly, we found that the semaphorin receptor Nrp-1 is expressed on the perivascular cells of the collecting lymphatic vessels. Treatment of mice in utero (E12.5-E16.5) with an antibody that blocks Sema3A binding to Nrp-1 but not with an antibody that blocks VEGF-A binding to Nrp-1 resulted in a complex phenotype of impaired lymphatic vessel function, enhanced perivascular cell coverage, and abnormal lymphatic vessel and valve morphology.
CONCLUSIONS: Together, these results reveal an unanticipated role of Sema3A-Nrp-1 signaling in the maturation of the lymphatic vascular network likely via regulating the perivascular cell coverage of the vessels thus affecting lymphatic vessel function and lymphatic valve development.
Keywords
Animals, Antibodies, Neutralizing/administration & dosage, Cell Lineage, Cell Movement, Cell Separation/methods, Cells, Cultured, Endothelial Cells/metabolism, Gene Expression Profiling/methods, Gestational Age, Humans, Lymphangiogenesis, Lymphatic Vessels/embryology, Lymphatic Vessels/metabolism, Mice, Mice, Inbred C57BL, Myocytes, Smooth Muscle/metabolism, Neuropilin-1/genetics, Neuropilin-1/immunology, Oligonucleotide Array Sequence Analysis, Pericytes/metabolism, Semaphorin-3A/genetics, Semaphorin-3A/metabolism, Signal Transduction, Vascular Endothelial Growth Factor A/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
20/12/2012 16:59
Last modification date
08/05/2019 17:33
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