Scar Wars


Skin is big business in cosmetics. The marketplace is flooded with products that claim to take care of our skin, and researchers around the globe are continually looking for ways to improve both skin's appearance and its condition. After all, skin is a highly sophisticated tissue. It has homeostatic properties, playing a vital role in regulating body temperature and hydration, and it provides a first, physical barrier to infection. What's more, it is able to repair itself after being damaged.

Appearance and condition of the skin do not always go hand-in-hand, though, and this repair process can result in unattractive scars. Mother Nature, it seems, has compromised aesthetics for rapid wound closure in the interests of survival of the organism, says Anie Philip (pictured above left), associate director at the Division of Surgical Research, McGill University.

Dr. Philip's research team of four graduate students, one postdoc, and a research assistant are investigating the role of a cytokine called transforming growth factor-beta (TGF-b) in homeostasis and skin tissue repair. More specifically, her research focuses on identifying molecules that may regulate the synthesis and activation of TGF-b in skin tissue, with the eventual aim of using these agents to promote skin repair and reduce scarring. The research recently received a significant financial boost when Philip was awarded the international 2002 L'Oréal Skin Grant, with a value of ?45,000. The cosmetics company L'Oréal, in collaboration with La Société Française de Dermatologie and La Société de Recherche Dermatologique, awards the annual Skin Grant to a scientist conducting clinical or basic research on normal skin and hair physiology.

From left to right: Dr. Béatrice Crickx, president of La Société Française de Dermatologie; Dr. Anie Philip, associate director of plastic surgery at the McGill University Health Centre; Dr. Hervé Bachelez, president of La Société de Recherche Dermatologique and Dr. Michèle Verschoore, L'Oréal Recherche.

TGF-b appears to help the healing of tissues through its involvement in the formation and deposition of collagen fibres around a wound site, resulting in a healthy scar tissue. However, like for many vital molecules, too much or too little TGF-b may have severe consequences: Too much can promote the debilitating build-up of excessive fibrous scar tissue and lead to eventual organ failure; but if it is deficient, as is often the case in diabetics, wound healing is impaired and the risk of infections increased.

TGF-b may be present in the skin under three forms, each representing a different state of activation and each performing a distinct function with regards to TGF-b signalling in skin cells. "One of our major objectives is to identify molecules which control the activation and signalling of TGF-b" Philip explains. Recent research findings in her lab suggest that factors such as steroids and oxygen supply can alter TGF-b bioavailability in the skin. Philip and her graduate students are exploring the possibility that these agents could be used to manipulate the ratio of the three distinct TGF-b molecules in skin, to promote better healing and produce more aesthetically appealing scars.

In addition to studying the effects of steroids and oxygen on skin, Philip's lab is working on yet another potential avenue for therapeutic manipulation of TGF-b to reduce scarring. They have identified a novel cell surface protein, r150, that interacts with TGF-b signalling receptors in human keratinocytes, a type of skin cell. The lab is now using in vivo studies to analyse the novel receptor's ability to act as an inhibitor of TGF-b signalling in skin, thus reducing excessive scarring. The project has attracted around half a million dollars of in-kind reagents from the U.S.-based pharmaceutical company, Genzyme Corp. Other organisations, such as the Canadian Institutes of Health Research and the Heart and Stroke Foundation, have also chipped in to fund Philip's research.

Philip's lab is one of only four in the country working in the field. Her interest in wound healing and skin repair stems from her postdoctoral research at the National Research Council's Biotechnology Research Institute in Quebec in 1988, where she studied the clearance of the molecules from the body. Her research now attracts MD/PhD students in plastic surgery as well as science students who, like Ann Marcoux, want to use their graduate research experience to eventually find a job within a cosmetics company.

"Our long-term goal is to understand the molecular mechanisms involved in TGF-b action in the context of tissue repair in general," Philip says. But if the benefits to the cosmetics industry are obvious, the skin research performed by Philip's lab goes far beyond the aesthetics of scarring. "These studies are highly relevant to promoting wound healing in healing-impaired patients, such as diabetics, the elderly, and people with venous stasis or pressure ulcers." Similarly, "tissue fibrosis [synthesis of too many collagen fibres] is a major medical problem with no satisfactory treatment options," she continues, "be it hypertrophic scarring which occurs in burn patients, keloids which occur more often in people with coloured skin, or lung, liver, or kidney fibrosis." She hopes that clinical trials with an emphasis on improving both aesthetics and function are only a few years down the road.

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