PUBLICATION

CD146 is required for VEGF-C-induced lymphatic sprouting during lymphangiogenesis

Authors
Yan, H., Zhang, C., Wang, Z., Tu, T., Duan, H., Luo, Y., Feng, J., Liu, F., Yan, X.
ID
ZDB-PUB-170809-6
Date
2017
Source
Scientific Reports   7: 7442 (Journal)
Registered Authors
Liu, Feng, Zhang, Chunxia
Keywords
Growth factor signalling, Lymphangiogenesis
MeSH Terms
  • Cell Proliferation
  • Mice
  • Vascular Endothelial Growth Factor C/metabolism*
  • Gene Knockdown Techniques
  • Lymphatic Vessels/cytology*
  • Lymphatic Vessels/metabolism
  • Animals
  • Extracellular Signal-Regulated MAP Kinases/metabolism
  • p38 Mitogen-Activated Protein Kinases/metabolism
  • Lymphangiogenesis*
  • Cell Line
  • CD146 Antigen/genetics
  • CD146 Antigen/metabolism
  • Humans
  • HEK293 Cells
  • Zebrafish
  • Cell Movement
  • Human Umbilical Vein Endothelial Cells
(all 18)
PubMed
28785085 Full text @ Sci. Rep.
Abstract
VEGF-C is essential for lymphangiogenesis during development and tumor progression. VEGFR-3 is the well-known cognate receptor of VEGF-C to regulate lymphatic migration and proliferation, but the receptor of VEGF-C in regulating lymphatic sprouting, the initiating step of lymphangiogenesis, still remains elusive. Here we use both in vitro and in vivo methods to demonstrate CD146 as a receptor of VEGF-C to regulate lymphangiogenesis, especially at the sprouting step. Mechanistically, CD146 selectively activates the downstream p38 kinase, upon VEGF-C stimulation, to regulate lymphatic sprouting. Moreover, CD146 can also activate ERK to mediate VEGF-C regulation of the subsequent proliferation and migration of lymphatic endothelial cells. In zebrafish embryos, knockdown or dysfunction of CD146 results in similar developmental defects in lymphatic sprouting, capillary network, parachordal lymphangioblast (PL), and thoracic duct (TD) similar to down-regulation of VEGF-C. Altogether, our data reveals a critical role of CD146 to mediate VEGF-C signaling pathway in lymphangiogenesis.
Genes / Markers
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ci5TgTransgenic Insertion
    y1TgTransgenic Insertion
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      Human Disease / Model
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      Sequence Targeting Reagents
      Target Reagent Reagent Type
      mcambMO3-mcambMRPHLNO
      vegfcMO1-vegfcMRPHLNO
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      Fish
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      Engineered Foreign Genes
      Marker Marker Type Name
      EGFPEFGEGFP
      mCherryEFGmCherry
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