PUBLICATION

ADAMTS3 activity is mandatory for embryonic lymphangiogenesis and regulates placental angiogenesis

Authors
Janssen, L., Dupont, L., Bekhouche, M., Noel, A., Leduc, C., Voz, M., Peers, B., Cataldo, D., Apte, S.S., Dubail, J., Colige, A.
ID
ZDB-PUB-151009-5
Date
2016
Source
Angiogenesis   19(1): 53-65 (Journal)
Registered Authors
Peers, Bernard, Voz, Marianne
Keywords
ADAMTS, Angiogenesis, Collagen, Development, Lymphangiogenesis, Placenta
MeSH Terms
  • ADAM Proteins/deficiency
  • ADAM Proteins/metabolism*
  • Animals
  • Blood Vessels/pathology
  • Cartilage/pathology
  • Collagen/metabolism
  • Edema/pathology
  • Embryo Loss/metabolism
  • Embryo Loss/pathology
  • Embryo, Mammalian/metabolism*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Homozygote
  • Immunohistochemistry
  • Liver/embryology
  • Liver/pathology
  • Lymphangiogenesis*
  • Mice
  • Mutation/genetics
  • Neovascularization, Physiologic*
  • Oligonucleotide Array Sequence Analysis
  • Placenta/blood supply*
  • Placenta/pathology
  • Pregnancy
  • Protein Processing, Post-Translational
  • Skin/pathology
  • Vascular Endothelial Growth Factor C/metabolism
PubMed
26446156 Full text @ Angiogenesis
Abstract
The only documented activity of a subclass of ADAMTS proteases comprising ADAMTS2, 3 and 14 is the cleavage of the aminopropeptide of fibrillar procollagens. A limited number of in vitro studies suggested that ADAMTS3 is mainly responsible for procollagen II processing in cartilage. Here, we created an ADAMTS3 knockout mouse (Adamts3(-/-)) model to determine in vivo the actual functions of ADAMTS3. Heterozygous Adamts3(+/-) mice were viable and fertile, but their intercrosses demonstrated lethality of Adamts3(-/-) embryos after 15 days of gestation. Procollagens I, II and III processing was unaffected in these embryos. However, a massive lymphedema caused by the lack of lymphatics development, an abnormal blood vessel structure in the placenta and a progressive liver destruction were observed. These phenotypes are most probably linked to dysregulation of the VEGF-C pathways. This study is the first demonstration that an aminoprocollagen peptidase is crucial for developmental processes independently of its primary role in collagen biology and has physiological functions potentially involved in several human diseases related to angiogenesis and lymphangiogenesis.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping