Progranulin deficiency exaggerates, whereas progranulin-derived Atsttrin attenuates, severity of dermatitis in mice

PGRN and its derived engineered protein, Atsttrin, were reported to antagonize TNF alpha and protect against inflammatory arthritis [Tang, W. et al. (2011) The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science 332 (6028) 478-484]. Here we found that PGRN level was also significantly elevated in skin inflammation. PGRN-/- mice exhibited more severe inflammation following induction of oxazolone (OXA). In contrast, recombinant Atsttrin protein effectively attenuated inflammation in mice dermatitis model. In addition, the protective role of PGRN and Atsttrin in dermatitis was probably due to their inhibition on NF-kappa B signaling. Collectively, PGRN, especially its derived engineered protein, Atsttrin, may represent a potential molecular target for prevention and treatment of inflammatory skin diseases. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.