CMG2/ANTXR2 regulates extracellular collagen VI which accumulates in hyaline fibromatosis syndrome.

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State: Public
Version: Final published version
Serval ID
serval:BIB_D06F5FC5430F
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
CMG2/ANTXR2 regulates extracellular collagen VI which accumulates in hyaline fibromatosis syndrome.
Journal
Nature communications
Author(s)
Bürgi J., Kunz B., Abrami L., Deuquet J., Piersigilli A., Scholl-Bürgi S., Lausch E., Unger S., Superti-Furga A., Bonaldo P., van der Goot F.G.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
12/06/2017
Peer-reviewed
Oui
Volume
8
Pages
15861
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Loss-of-function mutations in capillary morphogenesis gene 2 (CMG2/ANTXR2), a transmembrane surface protein, cause hyaline fibromatosis syndrome (HFS), a severe genetic disorder that is characterized by large subcutaneous nodules, gingival hypertrophy and severe painful joint contracture. Here we show that CMG2 is an important regulator of collagen VI homoeostasis. CMG2 loss of function promotes accumulation of collagen VI in patients, leading in particular to nodule formation. Similarly, collagen VI accumulates massively in uteri of Antxr2 <sup>-/-</sup> mice, which do not display changes in collagen gene expression, and leads to progressive fibrosis and sterility. Crossing Antxr2 <sup>-/-</sup> with Col6a1 <sup>-/-</sup> mice leads to restoration of uterine structure and reversion of female infertility. We also demonstrate that CMG2 may act as a signalling receptor for collagen VI and mediates its intracellular degradation.
Keywords
Animals, Collagen Type VI/metabolism, Female, Fibrosis/metabolism, Fibrosis/pathology, Humans, Hyalinosis, Systemic/metabolism, Matrix Metalloproteinases/metabolism, Mice, Mice, Knockout, Receptors, Peptide/genetics, Receptors, Peptide/metabolism, Receptors, Peptide/physiology, Uterus/metabolism, Uterus/pathology
Pubmed
Web of science
Open Access
Yes
Create date
22/06/2017 18:29
Last modification date
20/08/2019 16:50
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