Caspase-14 Protects Our Skin Against UVB And Dehydration

Main Category: Dermatology
Also Included In: Melanoma / Skin Cancer
Article Date: 23 May 2007 - 12:00 PDT

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Ultraviolet rays can be harmful to our skin and pave the way to the onset of skin cancers. VIB researchers connected to Ghent University have demonstrated that the caspase-14 protein - whose function has been unknown up to now - not only plays a role in maintaining the balance of moisture in the skin but also offers protection against UVB rays. Future strategies that increase the production of caspase-14 will open new possibilities for fortifying the skin as a barrier against all kinds of stress.

Sunbathing and the pernicious consequences for our skin

Sunlight is needed for the development of our bodies and minds. Still, we should not expose ourselves to it too often. The UV index provides an indication of the true intensity of the sun's rays and the risks that go along with them.

UV rays cause functional alterations in the most important components of our skin: the keratinocytes. In addition to causing normal sunburn and suppressing our immune responses, UVB damages the DNA in our cells, which can lead to cancer. In the last 15 years, the number of new cases of melanoma (the most dangerous skin cancer in Belgium) has practically doubled to 1500 cases per year.

Caspase-14

Caspases are proteins that are involved in inflammation reactions and in programmed cell death or apoptosis. Apoptosis is important in all stages of life. During embryonal development, for example, apoptosis ensures that undesirable or outmoded tissues disappear. In the mid-1990s, Peter Vandenabeele and his colleagues were able to isolate 9 caspase family members in mice. The properties and substrates of a number of caspases are already known. However, caspase-14 is a maverick in that it is found very specifically in the skin and is activated during the last stage of skin cell maturation. Due to the action of caspase-14, the outer epidermis of our skin contains dead cells that are released as flakes of skin.

Mice as model

To investigate the function of caspase-14, Geertrui Denecker and colleagues, under the direction of Wim Declercq and Peter Vandenabeele, developed knock-out mice that could no longer produce the protein. The shiny and lichenified skin of mice without caspase-14 is a sign that the composition of the skin's epidermis has been altered. The lack of caspase-14 causes defects in the processing of a protein that plays a major role in maintaining the skin's structure and balance of moisture, which can explain the skin's dehydration.

But one of our skin's most important functions is to protect us against UVB radiation. The researchers in Ghent have found that the filtering action of the epidermis of mice without caspase-14 decreases dramatically.

The skin as barrier

The absence of caspase-14 has very harmful effects on the skin's protective barrier function, which results in loss of water and diminished protection against UVB. This research sheds light on a portion of the mechanisms that operate in the skin's epidermis. The identification of molecules involved in caspase-14 dependent processes could well be important to the pharmaceutical industry, which is always seeking agents that prevent sunburn and ageing of the skin.

Relevant scientific publication

This research appears in the authoritative journal Nature Cell Biology (Denecker et al., Caspase-14 protects against epidermal UVB photo-damage and water loss, Nature Cell Biology, 2007).

Funding

This research has been funded by EU-FP6 Epistem, FWO, UGent, IUAP and VIB.

VIB, the Flanders Institute for Biotechnology, is a non-profit research institute in the life sciences. Some 1000 scientists and technicians conduct strategic basic research on the molecular mechanisms that control the functioning of the human body, plants, and micro-organisms. Through a close partnership with four Flemish universities - Ghent University, the Katholieke Universiteit Leuven, the University of Antwerp, and the Vrije Universiteit Brussel - and a solid investment program, VIB unites the forces of 65 research groups in a single institute. Their research aims at fundamentally extending the frontiers of our knowledge. Through its technology transfer activities, VIB strives to convert the research results into products for the benefit of consumers and patients. VIB also develops and distributes a broad range of scientifically substantiated information about all aspects of biotechnology.

www.vib.be

This research was conducted by Geertrui Denecker and colleagues under the direction of Wim Declercq. The project is a part of Peter Vandenabeele's Molecular Signalization and Cell Death research group in the VIB Department for Molecular Biomedical Research, UGent - under the direction of Frans Van Roy. (for more info, click here).