Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2005 Jan;116(1-2):51-61.
doi: 10.1007/s00439-004-1194-7. Epub 2004 Oct 23.

RGD-containing fibrillin-1 fragments upregulate matrix metalloproteinase expression in cell culture: a potential factor in the pathogenesis of the Marfan syndrome

Patrick Booms  1 , Reinhard Pregla, Andreas Ney, Frank Barthel, Dieter P Reinhardt, Angelika Pletschacher, Stefan Mundlos, Peter N Robinson
Affiliations

RGD-containing fibrillin-1 fragments upregulate matrix metalloproteinase expression in cell culture: a potential factor in the pathogenesis of the Marfan syndrome

Patrick Booms et al. Hum Genet. 2005 Jan.

Abstract

The Marfan syndrome (MFS), a relatively common autosomal dominant disorder of connective tissue, is caused by mutations in the gene for fibrillin-1 (FBN1). Fibrillin-1 is the main component of the 10- to 12-nm microfibrils that together with elastin form elastic fibers found in tissues such as the aortic media. Recently, FBN1 mutations have been shown to increase the susceptibility of fibrillin-1 to proteolysis in vitro, and other findings suggest that up-regulation of matrix metalloproteinases (MMP), as well as fragmentation of microfibrils, could play a role in the pathogenesis of MFS. In the present work, we have investigated the influence of fibrillin-1 fragments on the expression of MMP-1, MMP-2, and MMP-3 in a cell culture system. Cultured human dermal fibroblasts were incubated with several different recombinant fibrillin-1 fragments. The expression level of MMP-1, MMP-2, and MMP-3, was determined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), and the concentration of the corresponding proteins was estimated by quantitative Western blotting. Our results establish that treatment of cultured human dermal fibroblasts with recombinant fibrillin-1 fragments containing the arginine-glycine-aspartic acid (RGD) integrin-binding motif of fibrillin-1 induces up-regulation of MMP-1 and MMP-3. A similar effect was seen upon stimulation with a synthetic RGD peptide. The expression of MMP-2 was not influenced by treatment. Our results suggest the possibility that fibrillin fragments could themselves have pathogenic effects by leading to up-regulation of MMPs, which in turn may be involved in the progressive breakdown of microfibrils thought to play a role in MFS.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Matrix Biol. 1997 Mar;15(8-9):519-26 - PubMed
    1. Arch Ophthalmol. 2002 Jun;120(6):833-5 - PubMed
    1. Circulation. 1998 Nov 10;98(19 Suppl):II331-7; discussion II337-8 - PubMed
    1. J Biol Chem. 1997 Aug 29;272(35):22103-10 - PubMed
    1. Hum Mol Genet. 1993 Oct;2(10 ):1762 - PubMed

Publication types

LinkOut - more resources