Progranulin: A promising therapeutic target for rheumatoid arthritis

Progranulin (PGRN) is an autocrine growth factor with multiple functions. This review provides updates about the interplays of PGRN with extracellular matrix proteins, proteolytic enzymes, inflammatory cytokines, and cell surface receptors in cartilage and arthritis, with a special focus on the interaction between PGRN and TNF receptors (TNFR) and its implications in inflammatory arthritis. The paper also highlights Atsttrin, an engineered protein composed of three PGRN fragments that prevents inflammation in several inflammatory arthritis models. Identification of PGRN as a ligand of TNFR and an antagonist of TNF alpha signaling, together with the discovery of Atsttrin, not only betters our understanding of the pathogenesis of arthritis, but also provides new therapeutic interventions for various TNF alpha-mediated pathologies and conditions, including rheumatoid arthritis. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.