22 June 2012

Protein Molecule REG3A Lead To New And Better Treatment of Psoriasis


Psoriasis is a chronic inflammatory skin disease.

It is a common skin condition that is not contagious. Psoriasis is identified by dry, red patches of thick skin (called scales) resulting from rapid build up of skin cells. The redness and irritation are usually found around the skin of the elbows, knees, and scalp but can affect any area of the human body.

It is considered an autoimmune disease since the immune system mistakes the skin as a pathogen (infecting agent) and attacks by sending out signals to speed up the growth cycle of skin cells. The difference between psoriasis and other autoimmune disease is that unlike regular autoimmune diseases, there is no presence of any substance that activates the production of antibodies (antigen) to trigger an attack.

Skin cells are replaced about once a month in a process called cell turnover. These cells grow deep in the skin and rises above to replace old skin cells. In psoriasis, because of the signals from the immune system, the process is sped up and is done within days rather than in a month. The dead skin cells then accumulate on the skin surface as newer skin cells are pushed up due to the heightened cell turnover process.

Protein may be key to psoriasis and wound care

Psoriasis is an autoimmune disorder in which skin cells proliferate out of control. For some hard-to-heal wounds, the problem is just the opposite: Restorative skin cells don't grow well or fast enough. In a paper published in the June 21, 2012 issue of Immunity, researchers at the University of California, San Diego School of Medicine describe a molecule that may lead to new treatments for both problems.

An international team of scientists led by principal investigator Richard L. Gallo, MD, PhD, professor of medicine and chief of UC San Diego's Division of Dermatology, analyzed skin biopsies of patients with and without psoriasis, as well as the skin of mice with psoriasis and with wounds on their backs. They discovered that a molecule called regenerating islet-derived protein 3-alpha (REG3A) is highly expressed in skin cells during psoriasis and wound-healing, but not under normal skin conditions.

Video: Psoriasis


In tests on mice, researchers found that inhibiting REG3A slowed wound-healing but cleared up psoriasis, which is commonly characterized by patches of inflammation and white, scaly skin.

The scientists also noted that REG3A acts in concert with interleukin-17 (IL-17), an immune system protein involved in the signaling cascade which prompts skin cells to multiply in excess numbers. "IL-17 binds to receptors on skin cells and causes REG3A to be expressed, which then binds to another protein inside the cells that promotes cell growth," said first author Yuping Lai, PhD, professor of microbiology and immunity at East China Normal University in Shanghai.

Gallo said the discovery of REG3A's dual roles provides a new target for different therapies.

"A drug that inhibits the expression of REG3A could represent a more targeted way to treat psoriasis without the systemic immunosuppression problems of current treatments. Conversely, a drug that stimulates or mimics REG3A could boost cell growth and improve wound healing."

NOTE:
Funding for this research came, in part, from the National Institutes of Health (grants AR052728, AI052453, AI083358), the National Natural Science Foundation of China and the Science and Technology Commission of Shanghai Municipality.

RELATED LINKS

University of California - San Diego
Immunity
East China Normal University
National Institutes of Health
National Natural Science Foundation of China
Science and Technology Commission of Shanghai Municipality
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