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 inte...

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Bibliographic Details
Published in:FEBS letters 2011-12, Vol.585 (23), p.3675-3680
Main Author: Liu, Chuan-ju
Format: Article
Language:English
Subjects:
Animals
Arthritis, Rheumatoid - drug therapy
Arthritis, Rheumatoid - therapy
Atsttrin
Extracellular Matrix Proteins - metabolism
Humans
Inflammatory arthritis
Intercellular Signaling Peptides and Proteins - metabolism
Molecular Targeted Therapy
PGRN
Proteolysis
Recombinant Fusion Proteins - therapeutic use
TNFR
TNFα
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Summary: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 TNFα 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 TNFα-mediated pathologies and conditions, including rheumatoid arthritis.
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2011.04.065