Progranulin: A Key Player in Autoimmune Diseases

Overview

Journal Cytokine

Specialties Allergy & Immunology
Biology

Date 2016 Aug 17

PMID 27527809

Citations 60

Authors

Jinlong Jian

Guangfei Li

Aubryanna Hettinghouse

Chuanju Liu

Affiliations

Soon will be listed here.

Abstract

Autoimmune disease encompasses an array of conditions with a variety of presentations and the involvement of multiple organs. Though the etiologies of many autoimmune conditions are unclear, uncontrolled inflammatory immune response is believed to be a major cause of disease development and progression. Progranulin (PGRN), an anti-inflammatory molecule with therapeutic effect in inflammatory arthritis, was identified as an endogenous antagonist of TNFα by competitively binding to TNFR. PGRN exerts its anti-inflammatory activity through multiple pathways, including induction of T differentiation and IL-10 expression and inhibition of chemokine release from macrophages. In addition, the protective role of PGRN has also been demonstrated in osteoarthritis, inflammatory bowel disease, and psoriasis. Intriguingly, PGRN was reported to contribute to development of insulin resistance in high-fat diet induced diabetes. Emerging evidences indicate that PGRN may also be associated with various autoimmune diseases, including systemic lupus erythematous, systemic sclerosis, multiple sclerosis and Sjogren's syndrome. This review summarizes recent studies of PGRN as a novel target molecule in the field of autoimmune disease, and provides updated information to inspire future studies.

Citing Articles

Progranulin Protects Against Osteoporosis by Regulating Osteoclast and Osteoblast Balance via TNFR Pathway.

Wang S, Zhang H, Zhu Y, Zhou X, Zhai H, He Q J Cell Mol Med. 2025; 29(3):e70385.

PMID: 39910695 PMC: 11798871. DOI: 10.1111/jcmm.70385.

Blood-Based Biomarkers in Frontotemporal Dementia: A Narrative Review.

Liampas I, Kyriakoulopoulou P, Karakoida V, Kavvoura P, Sgantzos M, Bogdanos D Int J Mol Sci. 2024; 25(21).

PMID: 39519389 PMC: 11546606. DOI: 10.3390/ijms252111838.

Versatility of 14-3-3 proteins and their roles in bone and joint-related diseases.

Zhou R, Hu W, Ma P, Liu C Bone Res. 2024; 12(1):58.

PMID: 39406741 PMC: 11480210. DOI: 10.1038/s41413-024-00370-4.

Transcriptomic analysis reveals cross-talk genes between type 2 diabetes and recurrent benign paroxysmal positional vertigo.

Hui J, Zi D, Liang L, Ren X Heliyon. 2024; 10(15):e35209.

PMID: 39170394 PMC: 11336458. DOI: 10.1016/j.heliyon.2024.e35209.

Progranulin and Vaspin as Potential Novel Markers in the Etiology of Type 1 Diabetes in Children.

Jakubek-Kipa K, Galiniak S, Mazur A Medicina (Kaunas). 2024; 60(7).

PMID: 39064594 PMC: 11279224. DOI: 10.3390/medicina60071165.

References

Kimmerling K, Furman B, Mangiapani D, Moverman M, Sinclair S, Huebner J . Sustained intra-articular delivery of IL-1RA from a thermally-responsive elastin-like polypeptide as a therapy for post-traumatic arthritis. Eur Cell Mater. 2015; 29:124-39. PMC: 4358781. DOI: 10.22203/ecm.v029a10. View

Ichimura Y, Asano Y, Akamata K, Noda S, Taniguchi T, Takahashi T . Progranulin Overproduction Due to Fli-1 Deficiency Contributes to the Resistance of Dermal Fibroblasts to Tumor Necrosis Factor in Systemic Sclerosis. Arthritis Rheumatol. 2015; 67(12):3245-55. DOI: 10.1002/art.39312. View

Butler G, Dean R, Tam E, Overall C . Pharmacoproteomics of a metalloproteinase hydroxamate inhibitor in breast cancer cells: dynamics of membrane type 1 matrix metalloproteinase-mediated membrane protein shedding. Mol Cell Biol. 2008; 28(15):4896-914. PMC: 2493375. DOI: 10.1128/MCB.01775-07. View

Huang K, Chen A, Zhang X, Song Z, Xu H, Cao J . Progranulin is preferentially expressed in patients with psoriasis vulgaris and protects mice from psoriasis-like skin inflammation. Immunology. 2015; 145(2):279-87. PMC: 4427392. DOI: 10.1111/imm.12446. View

Abella V, Scotece M, Conde J, Lopez V, Pirozzi C, Pino J . The novel adipokine progranulin counteracts IL-1 and TLR4-driven inflammatory response in human and murine chondrocytes via TNFR1. Sci Rep. 2016; 6:20356. PMC: 4745010. DOI: 10.1038/srep20356. View

Thurner L, Zaks M, Preuss K, Fadle N, Regitz E, Ong M . Progranulin antibodies entertain a proinflammatory environment in a subgroup of patients with psoriatic arthritis. Arthritis Res Ther. 2013; 15(6):R211. PMC: 3978758. DOI: 10.1186/ar4406. View

Vercellino M, Fenoglio C, Galimberti D, Mattioda A, Chiavazza C, Binello E . Progranulin genetic polymorphisms influence progression of disability and relapse recovery in multiple sclerosis. Mult Scler. 2015; 22(8):1007-12. DOI: 10.1177/1352458515610646. View

Liu C, Li X, Gao W, Liu W, Liu D . Progranulin-derived Atsttrin directly binds to TNFRSF25 (DR3) and inhibits TNF-like ligand 1A (TL1A) activity. PLoS One. 2014; 9(3):e92743. PMC: 3961393. DOI: 10.1371/journal.pone.0092743. View

Yamamoto Y, Takemura M, Serrero G, Hayashi J, Yue B, Tsuboi A . Increased serum GP88 (Progranulin) concentrations in rheumatoid arthritis. Inflammation. 2014; 37(5):1806-13. DOI: 10.1007/s10753-014-9911-4. View

10.

Matsubara T, Mita A, Minami K, Hosooka T, Kitazawa S, Takahashi K . PGRN is a key adipokine mediating high fat diet-induced insulin resistance and obesity through IL-6 in adipose tissue. Cell Metab. 2012; 15(1):38-50. DOI: 10.1016/j.cmet.2011.12.002. View

11.

Flehmig G, Scholz M, Kloting N, Fasshauer M, Tonjes A, Stumvoll M . Identification of adipokine clusters related to parameters of fat mass, insulin sensitivity and inflammation. PLoS One. 2014; 9(6):e99785. PMC: 4072672. DOI: 10.1371/journal.pone.0099785. View

12.

Olson S, Furman B, Kraus V, Huebner J, Guilak F . Therapeutic opportunities to prevent post-traumatic arthritis: Lessons from the natural history of arthritis after articular fracture. J Orthop Res. 2015; 33(9):1266-77. PMC: 4529755. DOI: 10.1002/jor.22940. View

13.

Siakavellas S, Sfikakis P, Bamias G . The TL1A/DR3/DcR3 pathway in autoimmune rheumatic diseases. Semin Arthritis Rheum. 2015; 45(1):1-8. DOI: 10.1016/j.semarthrit.2015.02.007. View

14.

Xia Q, Zhu S, Wu Y, Wang J, Cai Y, Chen P . Intra-articular transplantation of atsttrin-transduced mesenchymal stem cells ameliorate osteoarthritis development. Stem Cells Transl Med. 2015; 4(5):523-31. PMC: 4414219. DOI: 10.5966/sctm.2014-0200. View

15.

de Munain A, Alzualde A, Gorostidi A, Otaegui D, Ruiz-Martinez J, Indakoetxea B . Mutations in progranulin gene: clinical, pathological, and ribonucleic acid expression findings. Biol Psychiatry. 2007; 63(10):946-52. DOI: 10.1016/j.biopsych.2007.08.015. View

16.

Zhao Y, Tian Q, Liu C . Progranulin deficiency exaggerates, whereas progranulin-derived Atsttrin attenuates, severity of dermatitis in mice. FEBS Lett. 2013; 587(12):1805-10. PMC: 3683372. DOI: 10.1016/j.febslet.2013.04.037. View

17.

Triebel J . Comment on: Richter et al. Serum levels of the adipokine progranulin depend on renal function. Diabetes Care 2013;36:410-414. Diabetes Care. 2013; 36(6):e83. PMC: 3661840. DOI: 10.2337/dc12-2275. View

18.

Cruts M, Gijselinck I, van der Zee J, Engelborghs S, Wils H, Pirici D . Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature. 2006; 442(7105):920-4. DOI: 10.1038/nature05017. View

19.

Zhao Y, Tian Q, Frenkel S, Liu C . The promotion of bone healing by progranulin, a downstream molecule of BMP-2, through interacting with TNF/TNFR signaling. Biomaterials. 2013; 34(27):6412-21. PMC: 3713419. DOI: 10.1016/j.biomaterials.2013.05.030. View

20.

Xu D, Suenaga N, Edelmann M, Fridman R, Muschel R, Kessler B . Novel MMP-9 substrates in cancer cells revealed by a label-free quantitative proteomics approach. Mol Cell Proteomics. 2008; 7(11):2215-28. PMC: 2577209. DOI: 10.1074/mcp.M800095-MCP200. View