Psoriasis and Wound Healing Gene Identified

A gene has been identified that regulates keratinocyte proliferation and differentiation after skin injury and, when overexpressed, can induce the autoimmune skin disorder psoriasis.

Investigators at the University of California, San Diego (USA) 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 reported in the June 21, 2012, online edition of the journal Immunity that regenerating islet-derived protein 3-alpha (REG3A) was highly expressed in keratinocytes during psoriasis and wound repair and in induced psoriatic skin lesions in mice. This gene encodes a pancreatic secretory protein that may be involved in cell proliferation or differentiation. The enhanced expression of this gene has been observed during pancreatic inflammation and liver carcinogenesis.

In experiments carried out on mice wound and psoriasis models, the investigators found that inhibition of REG3A slowed wound-healing but reversed psoriasis.

The expression of REG3A by keratinocytes was shown to be induced by interleukin-17 (IL-17) via activation of the keratinocyte-encoded IL-17 receptor A (IL-17RA). This activity acted to inhibit terminal differentiation and increased cell proliferation by binding to exostosin-like 3 (EXTL3) protein followed by activation of phosphatidylinositol 3 kinase (PI3K) and the kinase Akt (protein kinase B).

Senior author Dr. Richard L. Gallo, professor of medicine at the University of California, San Diego, 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.”

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University of California, San Diego