Progranulin: a Promising Therapeutic Target for Rheumatoid Arthritis

Overview

Journal FEBS Lett

Specialty Biochemistry

Date 2011 May 10

PMID 21550343

Citations 63

Authors

Chuan-Ju Liu

Affiliations

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Abstract

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.

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References

Munck Petersen C, Nielsen M, Jacobsen C, Tauris J, Jacobsen L, GLIEMANN J . Propeptide cleavage conditions sortilin/neurotensin receptor-3 for ligand binding. EMBO J. 1999; 18(3):595-604. PMC: 1171152. DOI: 10.1093/emboj/18.3.595. View

French M, Gomes Jr R, Timpl R, Hook M, Czymmek K, Farach-Carson M . Chondrogenic activity of the heparan sulfate proteoglycan perlecan maps to the N-terminal domain I. J Bone Miner Res. 2002; 17(1):48-55. PMC: 1774590. DOI: 10.1359/jbmr.2002.17.1.48. View

He Z, Ismail A, Kriazhev L, Sadvakassova G, Bateman A . Progranulin (PC-cell-derived growth factor/acrogranin) regulates invasion and cell survival. Cancer Res. 2002; 62(19):5590-6. View

Di Cesare P, Carlson C, Stolerman E, Hauser N, Tulli H, Paulsson M . Increased degradation and altered tissue distribution of cartilage oligomeric matrix protein in human rheumatoid and osteoarthritic cartilage. J Orthop Res. 1996; 14(6):946-55. DOI: 10.1002/jor.1100140615. View

He Z, Ong C, Halper J, Bateman A . Progranulin is a mediator of the wound response. Nat Med. 2003; 9(2):225-9. DOI: 10.1038/nm816. View

He Z, Bateman A . Progranulin (granulin-epithelin precursor, PC-cell-derived growth factor, acrogranin) mediates tissue repair and tumorigenesis. J Mol Med (Berl). 2003; 81(10):600-12. DOI: 10.1007/s00109-003-0474-3. View

Tangkeangsirisin W, Hayashi J, Serrero G . PC cell-derived growth factor mediates tamoxifen resistance and promotes tumor growth of human breast cancer cells. Cancer Res. 2004; 64(5):1737-43. DOI: 10.1158/0008-5472.can-03-2364. View

He Z, Bateman A . Progranulin gene expression regulates epithelial cell growth and promotes tumor growth in vivo. Cancer Res. 1999; 59(13):3222-9. View

Deng G, Zheng L, Chan F, Lenardo M . Amelioration of inflammatory arthritis by targeting the pre-ligand assembly domain of tumor necrosis factor receptors. Nat Med. 2005; 11(10):1066-72. DOI: 10.1038/nm1304. View

10.

Briggs M, Mortier G, Cole W, King L, Golik S, Bonaventure J . Diverse mutations in the gene for cartilage oligomeric matrix protein in the pseudoachondroplasia-multiple epiphyseal dysplasia disease spectrum. Am J Hum Genet. 1998; 62(2):311-9. PMC: 1376889. DOI: 10.1086/301713. View

11.

Feldmann M, Maini R . Lasker Clinical Medical Research Award. TNF defined as a therapeutic target for rheumatoid arthritis and other autoimmune diseases. Nat Med. 2003; 9(10):1245-50. DOI: 10.1038/nm939. View

12.

Kessenbrock K, Frohlich L, Sixt M, Lammermann T, Pfister H, Bateman A . Proteinase 3 and neutrophil elastase enhance inflammation in mice by inactivating antiinflammatory progranulin. J Clin Invest. 2008; 118(7):2438-47. PMC: 2430496. DOI: 10.1172/JCI34694. View

13.

Di Cesare P, Fang C, Leslie M, Tulli H, Perris R, Carlson C . Expression of cartilage oligomeric matrix protein (COMP) by embryonic and adult osteoblasts. J Orthop Res. 2000; 18(5):713-20. DOI: 10.1002/jor.1100180506. View

14.

Hecht J, Francomano C, Briggs M, Deere M, Conner B, Horton W . Linkage of typical pseudoachondroplasia to chromosome 19. Genomics. 1993; 18(3):661-6. DOI: 10.1016/s0888-7543(05)80370-2. View

15.

Feng J, Guo F, Jiang B, Zhang Y, Frenkel S, Wang D . Granulin epithelin precursor: a bone morphogenic protein 2-inducible growth factor that activates Erk1/2 signaling and JunB transcription factor in chondrogenesis. FASEB J. 2010; 24(6):1879-92. PMC: 2874481. DOI: 10.1096/fj.09-144659. View

16.

Neidhart M . Elevated serum prolactin or elevated prolactin/cortisol ratio are associated with autoimmune processes in systemic lupus erythematosus and other connective tissue diseases. J Rheumatol. 1996; 23(3):476-81. View

17.

Bongartz T, Orenstein R . Therapy: The risk of herpes zoster: another cost of anti-TNF therapy?. Nat Rev Rheumatol. 2009; 5(7):361-3. DOI: 10.1038/nrrheum.2009.120. View

18.

Liu C . The role of ADAMTS-7 and ADAMTS-12 in the pathogenesis of arthritis. Nat Clin Pract Rheumatol. 2008; 5(1):38-45. PMC: 4433145. DOI: 10.1038/ncprheum0961. View

19.

Mongiat M, Fu J, Oldershaw R, Greenhalgh R, Gown A, Iozzo R . Perlecan protein core interacts with extracellular matrix protein 1 (ECM1), a glycoprotein involved in bone formation and angiogenesis. J Biol Chem. 2003; 278(19):17491-9. DOI: 10.1074/jbc.M210529200. View

20.

Faustman D, Davis M . TNF receptor 2 pathway: drug target for autoimmune diseases. Nat Rev Drug Discov. 2010; 9(6):482-93. DOI: 10.1038/nrd3030. View