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Sci. Aging Knowl. Environ., 6 March 2002
Vol. 2002, Issue 9, p. nw30
[DOI: 10.1126/sageke.2002.9.nw30]

NOTEWORTHY ARTICLES

Thin-Skinned: Protein props up sagging skin (Dermatology)

Mitch Leslie

http://sageke.sciencemag.org/cgi/content/abstract/sageke;2002/9/nw30

Key Words: extracellular matrix • tenascin-X • collagen • Ehlers-Danlos syndrome • EDS • TNXB

Abstract: A protein implicated in a rare disorder of the skin and joints might help explain why Grandpa has slack jowls, drooping eyelids, and a wattle like your Thanksgiving turkey's. Fresh research suggests that the protein tones the skin by controlling how cells lay down the structural protein collagen.

Collagen deserves the award for best supporting protein. The cablelike fibers hold the body together, strengthening skin, bone, blood vessels, organs, teeth, and cartilage. Ehlers-Danlos syndrome (EDS), which affects about 1 in 5000 people, provokes progressive defects in collagen. The most common form of the syndrome makes the patient resemble "the rubber man in the circus, with really stretchy skin and joints that can move in ways that look like they ought to be painful," says cardiologist and geneticist James Bristow of the University of California, San Francisco. Rarely fatal, EDS often makes its sufferers miserable.

The syndrome intrigues gerontologists because the skin sags and becomes fragile, tearing easily--just as it does in old people. Several faulty genes can trigger EDS, causing cells to spin collagen fibers that are misshapen or that stick together. Recent work on families with EDS incriminated another gene--TNXB--which encodes the protein known as tenascin-X, but researchers didn't know how the protein might disrupt collagen.

To investigate tenascin-X's role, Mao and colleagues created mice that lack the TnxB gene. The rodents duplicated many of the symptoms of EDS. Their skin was loose and weak: To rip the skin of a knockout mouse required one-quarter as much force as in control animals. Although the strands of collagen were normal in size and shape, they were less abundant than in unmanipulated mice. The same thinning of collagen occurs in the skin of aging humans, Bristow says.

The investigators wanted to know whether the mice deficient in tenascin-X make abnormally small amounts of collagen. They nurtured collagen-making fibroblast cells from knockout and normal mice in culture and measured collagen production. The cells from the knockout animals extruded normal amounts of collagen. But the fibers weren't very good at entwining into a resilient mesh, or matrix, which suggests that tenascin-X helps guide this process.

The findings are significant because they conclusively tie TNXB and tenascin-X to EDS, says Peter Byers, an expert on the syndrome at the University of Washington, Seattle. The study will focus attention on the important question of how a squad of proteins that includes tenascin-X weaves the orderly extracellular matrix, which gives cartilage and skin added strength, he says.

EDS might resemble aging in many respects, but so far, no evidence links changes in tenascin-X activity to the faults of elderly skin, Bristow cautions. However, he says, our growing understanding of the mechanism that regulates the formation of collagen fibers might allow us to manipulate the process, perhaps restoring tone and springiness to drooping skin. That would lift the spirits of EDS patients, and it might lift a few jawlines as well.

--Mitch Leslie

J. Mao, G. Taylor, W. Dean, D. Wagner, V. Afzal, J. Lotz, E. Rubin, J. Bristow, Tenascin-X deficiency mimics Ehlers-Danlos syndrome in mice through alteration of collagen deposition. Nature Genet., 4 March 2002 [e-pub ahead of print]. [Abstract] [Full Text]

Citation: M. Leslie, Thin-Skinned: Protein props up sagging skin (Dermatology). Science's SAGE KE (6 March 2002), http://sageke.sciencemag.org/cgi/content/abstract/sageke;2002/9/nw30







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