Publication
Title
Mutations in Fibrillin-1 Cause Congenital Scleroderma: Stiff Skin Syndrome
Author
Abstract
The predisposition for scleroderma, defined as fibrosis and hardening of the skin, is poorly understood. We report that stiff skin syndrome (SSS), an autosomal dominant congenital form of scleroderma, is caused by mutations in the sole Arg-Gly-Asp sequence-encoding domain of fibrillin-1 that mediates integrin binding. Ordered polymers of fibrillin-1 (termed microfibrils) initiate elastic fiber assembly and bind to and regulate the activation of the profibrotic cytokine transforming growth factor-beta (TGF beta). Altered cell-matrix interactions in SSS accompany excessive microfibrillar deposition, impaired elastogenesis, and increased TGF beta concentration and signaling in the dermis. The observation of similar findings in systemic sclerosis, a more common acquired form of scleroderma, suggests broad pathogenic relevance.
Language
English
Source (journal)
Science translational medicine. - -
Publication
2010
ISSN
1946-6234
Volume/pages
2:23(2010), 10 p.
Article Reference
23ra20
ISI
000277304000003
Medium
E-only publicatie
Full text (Publisher's DOI)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
External links
Web of Science
Record
Identification
Creation 05.11.2018
Last edited 06.07.2021