A pair of studies supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) offers new clues into the body's processes of wound healing and hair follicle growth. The key player in both processes is a protein called keratin 17 (K17), part of a family of proteins called keratin intermediate filaments which belong to a network of fibers that maintain cell shape and strength. For years, K17 was thought to be involved only in the mechanical aspects of maintaining cell structure. Now, researcher Pierre A. Coulombe, Ph.D., and his colleagues at the Johns Hopkins University School of Medicine in Baltimore have found that K17 also plays a role in biochemical pathways of growth and healing. The implications, they say, could be far-reaching.

Coulombe and Xuemei Tong, a graduate student, found that mice lacking K17 fail to grow a healthy coat the first week after birth. They discovered that without the protein, mice go through one phase of their hair production cycle prematurely, leading to the death of follicle cells and fragile, thin hair. At the basis of this defect is enhanced signaling of an inflammatory chemical messenger called tumor necrosis factor alpha (TNFα), says Coulombe. "This implies that K17 normally promotes hair follicle growth by reducing the response of the follicles to the negative influence of TNFα."

"Many other keratins show an intriguing regulation in the hair follicles, raising the prospect that they too might play a role in hair cycling," he adds.

The role of K17 in wound healing is also an area of interest to Coulombe and his colleagues. In another study led by Seyun Kim, also a graduate student, they found evidence that K17 interacts with and regulates the function of 14-3-3 sigma, a protein with a key role in a major signaling pathway that helps control protein synthesis and cell growth. "This may only be part of the story"" says Coulombe, "as we find that K17 interacts with additional key effectors of protein synthesis and cell growth in keratinocytes [cells that produce keratin]." A better understanding of the fundamental mechanisms by which wound repair occurs in a timely fashion may lead to new therapeutic strategies to promote proper wound healing with minimal scarring. Moreover, these findings raise the possibility that K17 helps regulate cell growth in other settings in which it is expressed, such as developing skin, cycling hair follicles, and diseases such as psoriasis and cancer.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov.

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Tong X, Coulombe PA. Keratin 17 modulates hair follicle cycling in a TNFα-dependent fashion. Genes & Development 2006;20:1353-1364.

Kim S, Wong P, Coulombe PA. A keratin cytoskeletal protein regulates protein synthesis and epithelial cell growth. Nature 2006;441:362-365.

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