CD146 is required for VEGF-C-induced lymphatic sprouting during lymphangiogenesis.
Huiwen Yan1,2, Chunxia Zhang3,2, Zhaoqing Wang1
1Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Scientific Reports
|August 9, 2017
Summary
Vascular Endothelial Growth Factor-C (VEGF-C) signaling is crucial for lymphatic vessel formation. This study identifies CD146 as a novel receptor mediating VEGF-C's role in lymphatic sprouting and development.
Area of Science:
- Molecular Biology
- Developmental Biology
- Cell Biology
Background:
- Vascular Endothelial Growth Factor-C (VEGF-C) is vital for lymphangiogenesis.
- VEGFR-3 is the known receptor for VEGF-C, regulating lymphatic migration and proliferation.
- The receptor for VEGF-C in lymphatic sprouting remained unidentified.
Purpose of the Study:
- To identify the receptor mediating VEGF-C's role in lymphatic sprouting.
- To elucidate the downstream signaling pathways involved.
Main Methods:
- In vitro and in vivo experiments were conducted.
- Zebrafish embryos were used to study developmental defects.
- Kinase activation assays (p38, ERK) were performed.
Main Results:
- CD146 was identified as a receptor for VEGF-C in lymphangiogenesis.
- VEGF-C binding to CD146 activates p38 kinase, promoting lymphatic sprouting.
- CD146 also activates ERK, mediating VEGF-C-induced proliferation and migration.
- CD146 dysfunction in zebrafish mirrors VEGF-C down-regulation effects on lymphatic development.
Conclusions:
- CD146 is a critical receptor for VEGF-C signaling in lymphangiogenesis.
- CD146 plays a key role in the initiating step of lymphatic sprouting.
- This finding reveals a novel mechanism for VEGF-C in regulating lymphatic vessel formation.
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