Scleroderma pp 267-282 | Cite as

Fibrosis: Insights from the Stiff Skin Syndrome

  • Elizabeth E. GerberEmail author
  • Harry C. Dietz


Fibrillin-1 is a 350-kDa glycoprotein component of the extracellular matrix. It is a member of a small family of homologous glycoproteins that includes the fibulins and the latent TGFβ-binding proteins (LTBPs). Fibrillin-1 has 43 calcium-binding epidermal growth factor-like (cbEGF-like) domains, 4 noncalcium-binding EGF-like domains, 7 TGFβ-binding protein-like (TB) domains, 2 hybrid domains, unique N and C-termini, and a 58-amino-acid proline-rich sequence. Fibrillin-1 is an integral constituent of complex structures in the extracellular matrix called microfibrils (Sakai LY, Keene DR, Engvall E. Fibrillin, a new 350-kD glycoprotein, is a component of extracellular microfibrils. J Cell Biol. 1986;103(3536967):2499–509). By electron microscopy (EM), microfibrils extracted from tissues or cell culture have a “bead-on-a-string” appearance, with periodically spaced globular domains connected by linear arms (McDowall M, Edwards NM, Jahoda CA, Hynd PI. The role of activins and follistatins in skin and hair follicle development and function. Cytokine Growth Factor Rev. 2008;19(5–6):415–26; Xu MY, Porte J, Knox AJ, et al. Lysophosphatidic acid induces alphavbeta6 integrin-mediated TGF-beta activation via the LPA2 receptor and the small G protein G alpha(q). Am J Pathol. 2009;174(4):1264–79).


Fibrillin Fibroblast Fibrosis Integrin Skin fibrosis insights Stiff skin syndrome TGF-beta 


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Departments of Pediatrics, Medicine and Molecular Biology and Genetics and Institute of Genetic MedicineJohns Hopkins University School of Medicine and Howard Hughes Medical InstituteBaltimoreUSA

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