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Progranulin Is Associated with Disease Activity in Patients with Rheumatoid Arthritis

. 2015 ; 2015 () : 740357. [epub] 20150803

Language English Country United States Media print-electronic

Document type Journal Article, Research Support, Non-U.S. Gov't

OBJECTIVE: Progranulin (PGRN) is implicated in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to assess the relationship between PGRN and disease activity in RA. METHODS: PGRN levels were evaluated in patients with RA (n = 47) and OA (n = 42) and healthy controls (n = 41). Immunohistochemical analysis of PGRN in synovial tissues was performed. The association between PGRN and C-reactive protein (CRP), disease activity score (DAS28-CRP), and health assessment questionnaire (HAQ) was studied. RESULTS: Circulating PGRN was elevated in patients with RA and OA compared to healthy controls (227.1 ± 100.2 and 221.5 ± 102.5 versus 128.1 ± 34.7 ng/mL; P < 0.001). Synovial fluid levels of PGRN were higher in patients with RA compared to OA (384.5 ± 275.3 versus 241.4 ± 165.2 ng/mL; P = 0.002). PGRN expression was significantly upregulated in the synovial tissue of RA patients particularly in the inflammatory infiltrates. Serum PGRN levels correlated with DAS28 (r = 0.327, P = 0.049) and HAQ score (r = 0.323, P = 0.032), while synovial fluid PGRN correlated only with HAQ (r = 0.310, P = 0.043) in patients with RA. PGRN levels were not associated with CRP or autoantibodies. CONCLUSIONS: This study demonstrates increased PGRN expression at local sites of inflammation and association between PGRN levels, disease activity, and functional impairment in patients with RA.

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He Z., Bateman A. Progranulin (granulin-epithelin precursor, PC-cell-derived growth factor, acrogranin) mediates tissue repair and tumorigenesis. Journal of Molecular Medicine. 2003;81(10):600–612. doi: 10.1007/s00109-003-0474-3. PubMed DOI

Daniel R., He Z., Carmichael K. P., Halper J., Bateman A. Cellular localization of gene expression for progranulin. Journal of Histochemistry and Cytochemistry. 2000;48(7):999–1009. doi: 10.1177/002215540004800713. PubMed DOI

Bateman A., Bennett H. P. J. The granulin gene family: from cancer to dementia. BioEssays. 2009;31(11):1245–1254. doi: 10.1002/bies.200900086. PubMed DOI

He Z., Ong C. H. P., Halper J., Bateman A. Progranulin is a mediator of the wound response. Nature Medicine. 2003;9(2):225–229. doi: 10.1038/nm816. PubMed DOI

Kessenbrock K., Fröhlich L., Sixt M., et al. Proteinase 3 and neutrophil elastase enhance inflammation in mice by inactivating antiinflammatory progranulin. Journal of Clinical Investigation. 2008;118(7):2438–2447. doi: 10.1172/JC134694. PubMed DOI PMC

Zhu J., Nathan C., Jin W., et al. Conversion of proepithelin to epithelins: roles of SLPI and elastase in host defense and wound repair. Cell. 2002;111(6):867–878. doi: 10.1016/S0092-8674(02)01141-8. PubMed DOI

Yin F., Banerjee R., Thomas B., et al. Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice. Journal of Experimental Medicine. 2010;207(1):117–128. doi: 10.1084/jem.20091568. PubMed DOI PMC

Guo F., Lai Y., Tian Q., Lin E. A., Kong L., Liu C. Granulin-epithelin precursor binds directly to ADAMTS-7 and ADAMTS-12 and inhibits their degradation of cartilage oligomeric matrix protein. Arthritis and Rheumatism. 2010;62(7):2023–2036. doi: 10.1002/art.27491. PubMed DOI PMC

Xu K., Zhang Y., Ilalov K., et al. Cartilage oligomeric matrix protein associates with granulin-epithelin precursor (GEP) and potentiates GEP-stimulated chondrocyte proliferation. The Journal of Biological Chemistry. 2007;282(15):11347–11355. doi: 10.1074/jbc.M608744200. PubMed DOI

Feng J. Q., Guo F.-J., Jiang B.-C., et al. Granulin epithelin precursor: a bone morphogenic protein 2-inducible growth factor that activates Erk1/2 signaling and JunB transcription factor in chondrogenesis. The FASEB Journal. 2010;24(6):1879–1892. doi: 10.1096/fj.09-144659. PubMed DOI PMC

Tang W., Lu Y., Tian Q.-Y., et al. The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science. 2011;332(6028):478–484. doi: 10.1126/science.1199214. PubMed DOI PMC

Liu C.-J. Progranulin: a promising therapeutic target for rheumatoid arthritis. FEBS Letters. 2011;585(23):3675–3680. doi: 10.1016/j.febslet.2011.04.065. PubMed DOI PMC

Tanaka A., Tsukamoto H., Mitoma H., et al. Serum progranulin levels are elevated in patients with systemic lupus erythematosus, reflecting disease activity. Arthritis Research and Therapy. 2012;14(6, article R244) doi: 10.1186/ar4087. PubMed DOI PMC

Thurner L., Preuss K.-D., Fadle N., et al. Progranulin antibodies in autoimmune diseases. Journal of Autoimmunity. 2013;42:29–38. doi: 10.1016/j.jaut.2012.10.003. PubMed DOI

Arnett F. C., Edworthy S. M., Bloch D. A., et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis and Rheumatism. 1988;31(3):315–324. doi: 10.1002/art.1780310302. PubMed DOI

Cerezo L. A., Kuklová M., Hulejová H., et al. The level of fatty acid-binding protein 4, a novel adipokine, is increased in rheumatoid arthritis and correlates with serum cholesterol levels. Cytokine. 2013;64(1):441–447. doi: 10.1016/j.cyto.2013.05.001. PubMed DOI

Jüsten H.-P., Grünewald E., Totzke G., et al. Differential gene expression in synovium of rheumatoid arthritis and osteoarthritis. Molecular Cell Biology Research Communications. 2000;3(3):165–172. doi: 10.1006/mcbr.2000.0211. PubMed DOI

Yamamoto Y., Takemura M., Serrero G., et al. Increased serum GP88 (progranulin) concentrations in rheumatoid arthritis. Inflammation. 2014 doi: 10.1007/s10753-014-9911-4. PubMed DOI

Okura H., Yamashita S., Ohama T., et al. HDL/apolipoprotein A-I binds to macrophage-derived progranulin and suppresses its conversion into proinflammatory granulins. Journal of Atherosclerosis and Thrombosis. 2010;17(6):568–577. doi: 10.5551/jat.3921. PubMed DOI

Bonnet C. S., Walsh D. A. Osteoarthritis, angiogenesis and inflammation. Rheumatology. 2005;44(1):7–16. doi: 10.1093/rheumatology/keh344. PubMed DOI

Pearle A. D., Scanzello C. R., George S., et al. Elevated high-sensitivity C-reactive protein levels are associated with local inflammatory findings in patients with osteoarthritis. Osteoarthritis and Cartilage. 2007;15(5):516–523. doi: 10.1016/j.joca.2006.10.010. PubMed DOI

Stürmer T., Brenner H., Koenig W., Günther K.-P. Severity and extent of osteoarthritis and low grade systemic inflammation as assessed by high sensitivity C reactive protein. Annals of the Rheumatic Diseases. 2004;63(2):200–205. doi: 10.1136/ard.2003.007674. PubMed DOI PMC

Toncheva A., Remichkova M., Ikonomova K., Dimitrova P., Ivanovska N. Inflammatory response in patients with active and inactive osteoarthritis. Rheumatology International. 2009;29(10):1197–1203. doi: 10.1007/s00296-009-0864-0. PubMed DOI

Youn B.-S., Bang S.-I., Klöting N., et al. Serum progranulin concentrations may be associated with macrophage infiltration into omental adipose tissue. Diabetes. 2009;58(3):627–636. doi: 10.2337/db08-1147. PubMed DOI PMC

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