New discovery rarely runs smooth: an update on progranulin/TNFR interactions

Abstract

Progranulin (PGRN) is a growth factor implicated in various pathophysiological processes, including wound healing, inflammation, tumorigenesis, and neurodegeneration. It was previously reported that PGRN binds to tumor necrosis factor receptors (TNFR) and has therapeutic effects in inflammatory arthritis (Tang et. al, in Science 332:478−484, 2011); however, Chen et al. reported their inability to demonstrate the PGRN-TNFR interactions under their own conditions (Chen et. al, in J Neurosci 33:9202−9213, 2013). A letter-to-editor was then published by the original group in response to the Chen et al. paper that discussed the reasons for the latter’s inability to recapitulate the interactions. In addition, the group published follow-up studies that further reinforced and dissected the interactions of PGRNTNFR. Recently, the dispute about the legitimacy of PGRN-TNFR interactions appears to be finally settled with independent confirmations of these interactions in various conditions by numerous laboratories. This review presents a chronological update on the story of PGRN-TNFR interactions, highlighting the independent confirmations of these interactions in various diseases and conditions.

Key words： progranulin; Atsttrin; TNFR; DR3; TNF-α; TL1A

References

1 Aggarwal BB (2014) Editorial: balancing tumor necrosis factor receptor I and tumor necrosis factor receptor II jointly for joint inflammation. Arthritis Rheumatol 66: 2657−2660

2 Ahmed Z, Mackenzie IR, Hutton ML, Dickson DW (2007) Progranulin in frontotemporal lobar degeneration and neuroinflammation. J Neuroinflammation 4: 7

3 Almeida S, Zhou L, Gao FB (2011) Progranulin, a glycoprotein deficient in frontotemporal dementia, is a novel substrate of several protein disulfide isomerase family proteins. PloS One 6: e2 6454

4 Alquezar C, Encarnación A, Moreno F, Munain A, Martín-Requero Á (2015) Progranulin deficiency induces over activation of Wnt5a expression via TNFα/NF-κB pathway in peripheral cells from FTLD-linked GRN mutation carriers. J Psychiatry Neurosci (in press)

5 Baker CA, Manuelidis L (2003) Unique inflammatory RNA profiles of microglia in Creutzfeldt-Jakob disease. Proc Natl Acad Sci USA 100: 675−679

6 Baker M, Mackenzie IR, Pickering-Brown SM, Gass J, Rademakers R, Lindholm C, Snowden J, Adamson J, Sadovnick AD, Rollinson S (2006) Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17. Nature 442: 916−919

7 Bateman A, Bennett HP (2009) The granulin gene family: from cancer to dementia. BioEssays 31: 1245−1254

8 Bluml S, Binder NB, Niederreiter B, Polzer K, Hayer S, Tauber S, Schett G, Scheinecker C, Kollias G, Selzer E (2010) Antiinflammatory effects of tumor necrosis factor on hematopoietic cells in a murine model of erosive arthritis. Arthritis Rheum 62: 1608−1619

9 Bluml S, Scheinecker C, Smolen JS, Redlich K (2012) Targeting TNF receptors in rheumatoid arthritis. Int Immunol 24: 275−281

10 Bodmer JL, Burns K, Schneider P, Hofmann K, Steiner V, Thome M, Bornand T, Hahne M, Schroter M, Becker K (1997) TRAMP, a novel apoptosis-mediating receptor with sequence homology to tumor necrosis factor receptor 1 and Fas(Apo-1/CD95). Immunity 6: 79−88

11 Cavalli G, Dinarello CA (2015) Treating rheumatological diseases and co-morbidities with interleukin-1 blocking therapies. Rheumatology (Oxford).

12 Chen X, Chang J, Deng Q, Xu J, Nguyen TA, Martens LH, Cenik B, Taylor G, Hudson KF, Chung J (2013) Progranulin does not bind tumor necrosis factor (TNF) receptors and is not a direct regulator of TNF-dependent signaling or bioactivity in immune or neuronal cells. J Neurosci 33: 9202−9213

13 Chinnaiyan AM, O’Rourke K, Yu GL, Lyons RH, Garg M, Duan DR, Xing L, Gentz R, Ni J, Dixit VM (1996) Signal transduction by DR3, a death domain-containing receptor related to TNFR-1 and CD95. Science 274: 990−992

14 Conti P (1991) Interleukin-1 (IL-1) and interleukin-1 receptor antagonist (IL-1ra). Ann Med Int 142: 521−525

15 Croft M (2009) The role of TNF superfamily members in T-cell function and diseases. Nat Rev Immunol 9: 271−285

16 Cruts M, Gijselinck I, van der Zee J, Engelborghs S, Wils H, Pirici D, Rademakers R, Vandenberghe R, Dermaut B, Martin JJ (2006) Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21. Nature 442: 920−924

17 Diaz-Cueto L, Arechavaleta-Velasco F, Diaz-Arizaga A, Dominguez- Lopez P, Robles-Flores M (2012) PKC signaling is involved in the regulation of progranulin (acrogranin/PC-cell-derived growth factor/ granulin-epithelin precursor) protein expression in human ovarian cancer cell lines. Int J Gynecol Cancer 22: 945−950

18 Egashira Y, Suzuki Y, Azuma Y, Takagi T, Mishiro K, Sugitani S, Tsuruma K, Shimazawa M, Yoshimura S, Kashimata M (2013) The growth factor progranulin attenuates neuronal injury induced by cerebral ischemia-reperfusion through the suppression of neutrophil recruitment. J Neuroinflammation 10: 105

19 Faustman D, Davis M (2010) TNF receptor 2 pathway: drug target for autoimmune diseases. Nat Rev 9: 482−493

20 Frampton G, Invernizzi P, Bernuzzi F, Pae HY, Quinn M, Horvat D, Galindo C, Huang L, McMillin M, Cooper B (2012) Interleukin-6-driven progranulin expression increases cholangiocarcinoma growth by an Akt-dependent mechanism. Gut 61: 268−277

21 Grunke M, Schulze-Koops H (2006) Successful treatment of inflammatory knee osteoarthritis with tumour necrosis factor blockade. Ann Rheum Dis 65: 555−556

22 Guo Z, Li Q, Han Y, Liang Y, Xu Z, Ren T (2012) Prevention of LPSinduced acute lung injury in mice by progranulin. Mediat Inflammation 2012: 10

23 He Z, Ong CH, Halper J, Bateman A (2003) Progranulin is a mediator of the wound response. Nat Med 9: 225−229

24 Huang K, Chen A, Zhang X, Song Z, Xu H, Cao J, Yin Y (2015) Progranulin is preferentially expressed in patients with psoriasis vulgaris and protects mice from psoriasis-like skin inflammation. Immunology 145: 279−287

25 Hwang HJ, Jung TW, Hong HC, Choi HY, Seo JA, Kim SG, Kim NH, Choi KM, Choi DS, Baik SH (2013) Progranulin protects vascular endothelium against atherosclerotic inflammatory reaction via Akt/eNOS and nuclear factor-kappaB pathways. PloS One 8: e76679

26 Jian J, Konopka J, Liu C (2013a) Insights into the role of progranulin in immunity, infection, and inflammation. J Leukoc Biol 93: 199−208

27 Jian J, Zhao S, Tian Q, Gonzalez-Gugel E, Mundra JJ, Uddin SM, Liu B, Richbourgh B, Brunetti R, Liu CJ (2013b) Progranulin directly binds to the CRD2 and CRD3 of TNFR extracellular domains. FEBS Lett 587: 3428−3436

28 Kawase R, Ohama T, Matsuyama A, Matsuwaki T, Okada T, Yamashita T, Yuasa-Kawase M, Nakaoka H, Nakatani K, Inagaki M (2013) Deletion of progranulin exacerbates atherosclerosis in ApoE knockout mice. Cardiovasc Res 100: 125−133

29 Kessenbrock K, Frohlich L, Sixt M, Lammermann T, Pfister H, Bateman A, Belaaouaj A, Ring J, Ollert M, Fassler R (2008) Proteinase 3 and neutrophil elastase enhance inflammation in mice by inactivating antiinflammatory progranulin. J Clin Investig 118: 2438−2447

30 Kimmerling KA, Furman BD, Mangiapani DS, Moverman MA, Sinclair SM, Huebner JL, Chilkoti A, Kraus VB, Setton LA, Guilak F (2015) Sustained intra-articular delivery of IL-1RA from a thermally-responsive elastin-like polypeptide as a therapy for post-traumatic arthritis. Eur Cells Mater 29: 124−139; discussion 139−140

31 Klein DE, Nappi VM, Reeves GT, Shvartsman SY, Lemmon MA (2004) Argos inhibits epidermal growth factor receptor signalling by ligand sequestration. Nature 430: 1040−1044

32 Klein DE, Stayrook SE, Shi F, Narayan K, Lemmon MA (2008) Structural basis for EGFR ligand sequestration by Argos. Nature 453: 1271−1275

33 Li M, Liu Y, Xia F, Wu Z, Deng L, Jiang R, Guo FJ (2014) Progranulin is required for proper ER stress response and inhibits ER stressmediated apoptosis through TNFR2. Cell Signal 26: 1539−1548

34 Li H, Zhou B, Liu J, Li F, Li Y, Kang X, Sun H, Wu S (2015) Administration of progranulin (PGRN) triggers ER stress and impairs insulin sensitivity via PERK-eIF2alpha-dependent manner. Cell Cycle 14: 1893−1907

35 Liu CJ (2011) Progranulin: a promising therapeutic target for rheumatoid arthritis. FEBS Lett 585: 3675−3680

36 Liu CJ, Bosch X (2012) Progranulin: a growth factor, a novel TNFR ligand and a drug target. Pharmacol Ther 133: 124−132

37 Liu C, Li XX, Gao W, Liu W, Liu DS (2014) Progranulin-derived Atsttrin directly binds to TNFRSF25 (DR3) and inhibits TNF-like ligand 1A (TL1A) activity. PloS One 9: e92743

38 Liu J, Li H, Zhou B, Xu L, Kang X, Yang W, Wu S, Sun H (2015) PGRN induces impaired insulin sensitivity and defective autophagy in hepatic insulin resistance. Mol Endocrinol 29: 528−541

39 Lopez de Munain A, Alzualde A, Gorostidi A, Otaegui D, Ruiz-Martinez J, Indakoetxea B, Ferrer I, Perez-Tur J, Saenz A, Bergareche A (2008) Mutations in progranulin gene: clinical, pathological, and ribonucleic acid expression findings. Biol Psychiatry 63: 946−952

40 Ma CH, Lv Q, Yu YX, Zhang Y, Kong D, Niu KR, Yi CQ (2015) Protective effects of tumor necrosis factor-alpha blockade by adalimumab on articular cartilage and subchondral bone in a rat model of osteoarthritis. Brazilian journal of medical and biological research= Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica [et al], 0

41 Maksymowych WP, Russell AS, Chiu P, Yan A, Jones N, Clare T, Lambert RG (2012) Targeting tumour necrosis factor alleviates signs and symptoms of inflammatory osteoarthritis of the knee. Arthritis Res Ther 14: R206

42 Malaspina A, Kaushik N, de Belleroche J (2001) Differential expression of 14 genes in amyotrophic lateral sclerosis spinal cord detected using gridded cDNA arrays. J Neurochem 77: 132−145

43 Maynard JA, Lindquist NC, Sutherland JN, Lesuffleur A, Warrington AE, Rodriguez M, Oh SH (2009) Surface plasmon resonance for high-throughput ligand screening of membrane-bound proteins. Biotechnol J 4: 1542−1558

44 McCann FE, Perocheau DP, Ruspi G, Blazek K, Davies ML, Feldmann M, Dean JL, Stoop AA, Williams RO (2014) Selective tumor necrosis factor receptor I blockade is antiinflammatory and reveals immunoregulatory role of tumor necrosis factor receptor II in collagen-induced arthritis. Arthritis Rheumatol 66: 2728−2738

45 Myszka DG (1997) Kinetic analysis of macromolecular interactions using surface plasmon resonance biosensors. Curr Opin Biotechnol 8: 50−57

46 Olson SA, Furman BD, Kraus VB, Huebner JL, Guilak F (2015) Therapeutic opportunities to prevent post-traumatic arthritis: Lessons from the natural history of arthritis after articular fracture. J Orthop Res: Off Publ Orthop Res Soc 33: 1266−1277

47 Palfree RG, Bennett HP, Bateman A (2015) The evolution of the secreted regulatory protein progranulin. PloS One 10: e0133749

48 Reis CR, van Assen AH, Quax WJ, Cool RH (2011) Unraveling the binding mechanism of trivalent tumor necrosis factor ligands and their receptors. Mol Cell Proteom: MCP 10(M110): 002808

49 Scott LJ (2014) Etanercept: a review of its use in autoimmune inflammatory diseases. Drugs 74: 1379−1410

50 Serrero G (2003) Autocrine growth factor revisited: PC-cell-derived growth factor (progranulin), a critical player in breast cancer tumorigenesis. Biochem Biophys Res Commun 308: 409−413

51 Sfikakis PP, Tsokos GC (2011) Towards the next generation of anti-TNF drugs. Clin Immunol 141: 231−235

52 Tadagavadi RK, Reeves WB (2015) NODding off in acute kidney injury with progranulin? Kidney Int 87: 873−875

53 Tang W, Lu Y, Tian QY, Zhang Y, Guo FJ, Liu GY, Syed NM, Lai Y, Lin EA, Kong L (2011) The growth factor progranulin binds to TNF receptors and is therapeutic against inflammatory arthritis in mice. Science 332: 478−484

54 Thurner L, Preuss KD, Fadle N, Regitz E, Klemm P, Zaks M, Kemele M, Hasenfus A, Csernok E, Gross WL (2013a) Progranulin antibodies in autoimmune diseases. J Autoimmun 42: 29−38

55 Thurner L, Zaks M, Preuss KD, Fadle N, Regitz E, Ong MF, Pfreundschuh M, Assmann G (2013b) Progranulin antibodies entertain a proinflammatory environment in a subgroup of patients with psoriatic arthritis. Arthritis Res Ther 15: R211

56 Thurner L, Stoger E, Fadle N, Klemm P, Regitz E, Kemele M, Bette B, Held G, Dauer M, Lammert F (2014) Proinflammatory progranulin antibodies in inflammatory bowel diseases. Dig Dis Sci 59: 1733−1742

57 Thurner L, Fadle N, Regitz E, Kemele M, Klemm P, Zaks M, Stoger E, Bette B, Carbon G, Zimmer V (2015) The molecular basis for development of proinflammatory autoantibodies to progranulin. J Autoimmun 61: 17−28

58 Tian QY, Zhao YP, Liu CJ (2012) Modified yeast-two-hybrid system to identify proteins interacting with the growth factor progranulin. J Vis Exp.

59 Tian Q, Zhao S, Liu C (2014a) A solid-phase assay for studying direct binding of progranulin to TNFR and progranulin antagonism of TNF/TNFR interactions. Methods Mol Biol 1155: 163−172

60 Tian Q, Zhao Y, Mundra JJ, Gonzalez-Gugel E, Jian J, Uddin SM, Liu C (2014b) Three TNFR-binding domains of PGRN act independently in inhibition of TNF-alpha binding and activity. Front Biosci (Landmark Ed) 19: 1176−1185

61 Urech DM, Feige U, Ewert S, Schlosser V, Ottiger M, Polzer K, Schett G, Lichtlen P (2010) Anti-inflammatory and cartilageprotecting effects of an intra-articularly injected anti-TNF{alpha} single-chain Fv antibody (ESBA105) designed for local therapeutic use. Ann Rheum Dis 69: 443−449

62 Van Damme P, Van Hoecke A, Lambrechts D, Vanacker P, Bogaert E, van Swieten J, Carmeliet P, Van Den Bosch L, Robberecht W (2008) Progranulin functions as a neurotrophic factor to regulate neurite outgrowth and enhance neuronal survival. J Cell Biol 181: 37−41

63 van der Merwe PA, Brown MH, Davis SJ, Barclay AN (1993) Affinity and kinetic analysis of the interaction of the cell adhesion molecules rat CD2 and CD48. EMBO J 12: 4945−4954

64 Verbruggen G, Wittoek R, Vander Cruyssen B, Elewaut D (2012) Tumour necrosis factor blockade for the treatment of erosive osteoarthritis of the interphalangeal finger joints: a double blind, randomised trial on structure modification. Ann Rheum Dis 71: 891−898

65 Vercellino M, Grifoni S, Romagnolo A, Masera S, Mattioda A, Trebini C, Chiavazza C, Caligiana L, Capello E, Mancardi GL (2011) Progranulin expression in brain tissue and cerebrospinal fluid levels in multiple sclerosis. Mult Scler 17: 1194−1201

66 Vezina A, Vaillancourt-Jean E, Albarao S, Annabi B (2014) Mesenchymal stromal cell ciliogenesis is abrogated in response to tumor necrosis factor-alpha and requires NF-kappaB signaling. Cancer Lett 345: 100−105

67 Wang C, Luo X, Li P, Chen X, Zhou H, Zhang T (2015a) An improved method of GST-pull down based on fluorescence detection and its application to the analysis of the interaction between atsttrin and TNFR2. J Tianjin Univ Sci Technol 30: 34−40

68 Wang Q, Xia Q, Wu Y, Zhang X, Wen F, Chen X, Zhang S, Heng BC, He Y, Ouyang HW(2015b) 3D-printed atsttrin-incorporated alginate/hydroxyapatite scaffold promotes bone defect regeneration with tnf/tnfr signaling involvement. Adv Healthc Mater 4: 1701−1708

69 Wei F, Zhang Y, Jian J, Mundra JJ, Tian Q, Lin J, Lafaille JJ, Tang W, Zhao W, Yu X (2014a) PGRN protects against colitis progression in mice in an IL-10 and TNFR2 dependent manner. Sci Rep 4: 7023

70 Wei F, Zhang Y, Zhao W, Yu X, Liu CJ (2014b) Progranulin facilitates conversion and function of regulatory T cells under inflammatory conditions. PloS One 9: e112110

71 Wu H, Siegel RM (2011) Medicine. Progranulin resolves inflammation. Science 332: 427−428

72 Xia Q, Zhu S, Wu Y, Wang J, Cai Y, Chen P, Li J, Heng BC, Ouyang HW, Lu P (2015) Intra-articular transplantation of atsttrin-transduced mesenchymal stem cells ameliorate osteoarthritis development. Stem Cells Transl Med 4: 523−531

73 Yamamoto Y, Takemura M, Serrero G, Hayashi J, Yue B, Tsuboi A, Kubo H, Mitsuhashi T, Mannami K, Sato M (2014) Increased serum GP88 (Progranulin) concentrations in rheumatoid arthritis. Inflammation 37: 1806−1813

74 Yin F, Banerjee R, Thomas B, Zhou P, Qian L, Jia T, Ma X, Ma Y, Iadecola C, Beal MF (2010) Exaggerated inflammation, impaired host defense, and neuropathology in progranulin-deficient mice. J Exp Med 207: 117−128

75 Zhang Q, Lv H, Chen A, Liu F, Wu X (2012) Efficacy of infliximab in a rabbit model of osteoarthritis. Connect Tissue Res 53: 355−358

76 Zhao YP, Tian QY, Frenkel S, Liu CJ (2013a) The promotion of bone healing by progranulin, a downstream molecule of BMP-2, through interacting with TNF/TNFR signaling. Biomaterials 34: 6412−6421

77 Zhao YP, Tian QY, Liu CJ (2013b) Progranulin deficiency exaggerates, whereas progranulin-derived Atsttrin attenuates, severity of dermatitis in mice. FEBS Lett 587: 1805−1810

78 Zhao YP, Liu B, Tian QY, Wei JL, Richbourgh B, Liu CJ (2014) Progranulin protects against osteoarthritis through interacting with TNF-α and β-Catenin signalling. Ann Rheum Dis.

79 Zheng Y, Brady OA, Meng PS, Mao Y, Hu F (2011) C-terminus of progranulin interacts with the beta-propeller region of sortilin to regulate progranulin trafficking. PloS One 6: e21023

80 Zhou M, Tang W, Fu Y, Xu X, Wang Z, Lu Y, Liu F, Yang X, Wei X, Zhang Y (2015) Progranulin protects against renal ischemia/ reperfusion injury in mice. Kidney Int 87: 918−929

81 Zhu J, Nathan C, Jin W, Sim D, Ashcroft GS, Wahl SM, Lacomis L, Erdjument-Bromage H, Tempst P, Wright CD (2002) Conversion of proepithelin to epithelins: roles of SLPI and elastase in host defense and wound repair. Cell 111: 867−878