ADAMTS3 activity is mandatory for embryonic lymphangiogenesis and regulates placental angiogenesis
By Lauriane Janssen, Laura Dupont, M. Bekhouche, A. Noel, C. Leduc, M. Voz, B. Peers, D. Cataldo, S. Apte, Johanne Dubail and 1 more. 2015
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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.
Subfields: Molecular Biology, Oncology, Pathology and Forensic Medicine
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Citations in the corpus
- A Disintegrin and Metalloproteinase (ADAM) and ADAM with Thrombospondin Motifs (ADAMTS) Family in Vascular Biology and Disease (2019, background): “ADAMTS-3 could cleave and activate the substrate pro-VEGF-C into active VEGF-C and in turn play a role in embryonic lymphangiogenesis and the regulation of placental angiogenesis [107].”
- Secreted Metalloproteinase ADAMTS-3 Inactivates Reelin (2017, background): “We also noted the skin edema of embryonic ADAMTS-3 mice, as shown in the previous studies (Bui et al., 2016; Janssen et al., 2016).”
- ADAMTS proteins in human disorders (2018, background): “Adamts3-deficient mouse embryos do not survive past 15 days of gestation owing to severe lymphedema resulting from lack of lymphangiogenesis [34].”