Dynamic natures of the skin that control when a cut or scrape requires healing are vital for sustaining the skin's integrity. However if they get unruly, they can result in complications in the form of psoriasis and other skin disorders. Researchers reporting on June 21st in the Cell Press journal Immunity have now uncovered key information on how cells are stimulated to multiply during these processes. The information might be used to develop new treatments for psoriasis and hard-to-heal skin wounds.
For their studies, the scientists analyzed skin biopsies from individuals with and without psoriasis as well as the skin of mice with wounds on their backs and mice with psoriasis-like pathology. They found that a molecule called regenerating islet-derived protein 3-alpha (REG3A) is highly expressed in skin cells during psoriasis and wound repair, but not under normal skin conditions. Blocking REG3A delayed wound healing and cleared up psoriasis-like pathology in mice. The researchers also revealed the cascade of molecules that appear to act in conjunction with REG3A. Specifically, interleukin-17 (IL-17) binds to the IL-17 receptor A on skin cells and causes REG3A to be expressed; then REG3A binds to the exostosin-like 3 protein within cells, which activates certain enzymes that coax the cells to continue multiplying.
Previous research indicates that IL-17 is abundant in patients with psoriasis, and treatments that target the IL-17 pathway lessen their symptoms. "REG3A is stimulated by proteins known to be important to the pathogenesis of psoriasis. Therefore, REG3A appears to be the link between these proteins and the excess proliferation of skin cells that occurs in psoriasis," says first and corresponding author Dr. Yuping Lai, from the East China Normal University.
The findings offer potential targets for therapy. "A drug that inhibits REG3A would represent a more targeted way to treat psoriasis and avoid the systemic immunosuppression found with current therapy. Also, a drug that stimulates or mimics REG3A could be used to improve wound healing," says senior author Dr. Richard Gallo, from the University of California, San Diego.
Somewhat mysteriously, REG3A is also secreted by cells within the intestines and internal organs, where it has antimicrobial properties.