Soluble Fn14 Is Detected and Elevated in Mouse and Human Kidney Disease

M Nusrat Sharif, Gabriela Campanholle, Eva E Nagiec, Ju Wang, Jameel Syed, Shawn P O'Neil, Yutian Zhan, Karrie Brenneman, Bruce Homer, Hendrik Neubert, Riyez Karim, Nick Pullen, Steven M Evans, Margaret Fleming, Priya Chockalingam, Lih-Ling Lin, M Nusrat Sharif, Gabriela Campanholle, Eva E Nagiec, Ju Wang, Jameel Syed, Shawn P O'Neil, Yutian Zhan, Karrie Brenneman, Bruce Homer, Hendrik Neubert, Riyez Karim, Nick Pullen, Steven M Evans, Margaret Fleming, Priya Chockalingam, Lih-Ling Lin

Abstract

The cytokine TWEAK and its cognate receptor Fn14 are members of the TNF/TNFR superfamily and are upregulated in tissue injury to mediate local tissue responses including inflammation and tissue remodeling. We found that in various models of kidney disease, Fn14 expression (mRNA and protein) is upregulated in the kidney. These models include: lupus nephritis mouse models (Nephrotoxic serum Transfer Nephritis and MRL.Faslpr/lpr), acute kidney injury models (Ischemia reperfusion injury and Folic acid injury), and a ZSF-1 diabetic nephropathy rat model. Fn14 expression levels correlate with disease severity as measured by disease histology. We have also shown for the first time the detection of soluble Fn14 (sFn14) in the urine and serum of mice. Importantly, we found the sFn14 levels are markedly increased in the diseased mice and are correlated with disease biomarkers including proteinuria and MCP-1. We have also detected sFn14 in human plasma and urine. Moreover, sFn14 levels, in urine are significantly increased in DN patients and correlated with proteinuria and MCP-1 levels. Thus our data not only confirm the up-regulation of Fn14/TWEAK pathway in kidney diseases, but also suggest a novel mechanism for its regulation by the generation of sFn14. The correlation of sFn14 levels and disease severity suggest that sFn14 may serve as a potential biomarker for both acute and chronic kidney diseases.

Conflict of interest statement

Competing Interests: This work was funded, supported, and performed using Pfizer resources. All authors were employed by Pfizer Inc. during the course of this study. There are no products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Fn14 expression in kidney.
Fig 1. Fn14 expression in kidney.
A) Fn14 mRNA expression is upregulated in disease vs vehicle in the NTN model (8% and 32% vs vehicle; pp = 0.0008), R2 = 0.914 E) Fn14 mRNA expression is increased with progression of disease in MRL/lpr mice spontaneous mouse model of Lupus Nephritis. Kidneys from MRL/lpr mice were harvested at 22 weeks of age. Aged matched controls were kidneys from MRL/MPJ mice- comparable strain that does not develop Lupus Nephritis. F) IHC showing Fn14 expression in kidney of MRL/lpr model. Fn14 expression was most prominent in arterioles and glomerulus. G) Strong association of Fn14 with inflammation score in MRL/lpr model. Linear regression plot showing correlation of Fn14 expression with inflammation (p<0.0001) and R2 = 0.63.
Fig 2. Fn14 concentration is increased in…
Fig 2. Fn14 concentration is increased in NTN model of kidney injury.
(A) Increased concentration of Fn14 was detected in serum of mice injected with nephrotoxic serum (NTS) (vehicle vs NTS-**p = 0.006, Mann-Whitney test). Serum analysis was performed at the end of the study at 21 days. (B) Rapid increase in Fn14 concentration in urine (closed circles) apparent two days post NTS injection, was accompanied by development of proteinuria (closed triangles), and remained elevated through the duration of the study. (C) Urinary Fn14 strongly correlated with urinary albumin (r = 0.8803; p

Fig 3. Fn14 is upregulated in Folic…

Fig 3. Fn14 is upregulated in Folic Acid induced acute kidney injury.

Mice were systemically…

Fig 3. Fn14 is upregulated in Folic Acid induced acute kidney injury.
Mice were systemically dosed with either vehicle or FA. (A) BUN and (B) Urine microalbumin are increased in FA treated mice 24h after dosing. Histology from (C) vehicle control kidney and (D) FA-treated mice show tubular dilatation and attenuation in FA dosed kidneys, indicating acute kidney injury. (E) sFn14 in serum and (F) sFn14 in urine is increased in FA-treated mice 24h after dosing. (G) qRT-PCR shows up-regulation of Fn14 mRNA in FA induced AKI kidneys. IHC from vehicle control kidney (H) and (I) FA-treated mice shows increased Fn14 immuno-reactivity in tubular epithelia of FA dosed mouse kidneys.

Fig 4. Fn14 and TWEAK expression in…

Fig 4. Fn14 and TWEAK expression in DN.

A total of sixty male, 8-week-old ZSF1…

Fig 4. Fn14 and TWEAK expression in DN.
A total of sixty male, 8-week-old ZSF1 obese and lean littermates were used in this study. (A) Urine levels of sFn14 and mRNA expression in kidney from ZSF1 lean (control) and obese (disease) rats (lean vs obese *p
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    1. Wiley SR, Cassiano L, Lofton T, Davis-Smith T, Winkles JA, Lindner V, et al. A novel TNF receptor family member binds TWEAK and is implicated in angiogenesis. Immunity. 2001;15(5):837–46. . - PubMed
    1. Winkles JA. The TWEAK-Fn14 cytokine-receptor axis: discovery, biology and therapeutic targeting. Nature reviews Drug discovery. 2008;7(5):411–25. 10.1038/nrd2488 - DOI - PMC - PubMed
    1. Nakayama M, Ishidoh K, Kojima Y, Harada N, Kominami E, Okumura K, et al. Fibroblast growth factor-inducible 14 mediates multiple pathways of TWEAK-induced cell death. Journal of immunology. 2003;170(1):341–8. . - PubMed
    1. Justo P, Sanz AB, Sanchez-Nino MD, Winkles JA, Lorz C, Egido J, et al. Cytokine cooperation in renal tubular cell injury: the role of TWEAK. Kidney international. 2006;70(10):1750–8. 10.1038/sj.ki.5001866 . - DOI - PubMed
    1. Weinberg JM. TWEAK-Fn14 as a mediator of acute kidney injury. Kidney international. 2011;79(2):151–3. 10.1038/ki.2010.435 - DOI - PMC - PubMed
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Fig 3. Fn14 is upregulated in Folic…
Fig 3. Fn14 is upregulated in Folic Acid induced acute kidney injury.
Mice were systemically dosed with either vehicle or FA. (A) BUN and (B) Urine microalbumin are increased in FA treated mice 24h after dosing. Histology from (C) vehicle control kidney and (D) FA-treated mice show tubular dilatation and attenuation in FA dosed kidneys, indicating acute kidney injury. (E) sFn14 in serum and (F) sFn14 in urine is increased in FA-treated mice 24h after dosing. (G) qRT-PCR shows up-regulation of Fn14 mRNA in FA induced AKI kidneys. IHC from vehicle control kidney (H) and (I) FA-treated mice shows increased Fn14 immuno-reactivity in tubular epithelia of FA dosed mouse kidneys.
Fig 4. Fn14 and TWEAK expression in…
Fig 4. Fn14 and TWEAK expression in DN.
A total of sixty male, 8-week-old ZSF1 obese and lean littermates were used in this study. (A) Urine levels of sFn14 and mRNA expression in kidney from ZSF1 lean (control) and obese (disease) rats (lean vs obese *p

References

    1. Wiley SR, Cassiano L, Lofton T, Davis-Smith T, Winkles JA, Lindner V, et al. A novel TNF receptor family member binds TWEAK and is implicated in angiogenesis. Immunity. 2001;15(5):837–46. .
    1. Winkles JA. The TWEAK-Fn14 cytokine-receptor axis: discovery, biology and therapeutic targeting. Nature reviews Drug discovery. 2008;7(5):411–25. 10.1038/nrd2488
    1. Nakayama M, Ishidoh K, Kojima Y, Harada N, Kominami E, Okumura K, et al. Fibroblast growth factor-inducible 14 mediates multiple pathways of TWEAK-induced cell death. Journal of immunology. 2003;170(1):341–8. .
    1. Justo P, Sanz AB, Sanchez-Nino MD, Winkles JA, Lorz C, Egido J, et al. Cytokine cooperation in renal tubular cell injury: the role of TWEAK. Kidney international. 2006;70(10):1750–8. 10.1038/sj.ki.5001866 .
    1. Weinberg JM. TWEAK-Fn14 as a mediator of acute kidney injury. Kidney international. 2011;79(2):151–3. 10.1038/ki.2010.435
    1. Zhao Z, Burkly LC, Campbell S, Schwartz N, Molano A, Choudhury A, et al. TWEAK/Fn14 interactions are instrumental in the pathogenesis of nephritis in the chronic graft-versus-host model of systemic lupus erythematosus. Journal of immunology. 2007;179(11):7949–58. .
    1. Molano A, Lakhani P, Aran A, Burkly LC, Michaelson JS, Putterman C. TWEAK stimulation of kidney resident cells in the pathogenesis of graft versus host induced lupus nephritis. Immunol Lett. 2009;125(2):119–28. 10.1016/j.imlet.2009.06.010 .
    1. Sanz AB, Sanchez-Nino MD, Izquierdo MC, Jakubowski A, Justo P, Blanco-Colio LM, et al. Tweak induces proliferation in renal tubular epithelium: a role in uninephrectomy induced renal hyperplasia. Journal of cellular and molecular medicine. 2009;13(9B):3329–42. 10.1111/j.1582-4934.2009.00766.x
    1. Sanz AB, Sanchez-Nino MD, Ortiz A. TWEAK, a multifunctional cytokine in kidney injury. Kidney international. 2011;80(7):708–18. 10.1038/ki.2011.180 .
    1. Xia Y, Campbell SR, Broder A, Herlitz L, Abadi M, Wu P, et al. Inhibition of the TWEAK/Fn14 pathway attenuates renal disease in nephrotoxic serum nephritis. Clinical immunology. 2012;145(2):108–21. 10.1016/j.clim.2012.08.008
    1. Sanchez-Nino MD, Poveda J, Sanz AB, Mezzano S, Carrasco S, Fernandez-Fernandez B, et al. Fn14 in podocytes and proteinuric kidney disease. Biochim Biophys Acta. 2013;1832(12):2232–43. 10.1016/j.bbadis.2013.08.010 .
    1. Sanz AB, Izquierdo MC, Sanchez-Nino MD, Ucero AC, Egido J, Ruiz-Ortega M, et al. TWEAK and the progression of renal disease: clinical translation. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association—European Renal Association. 2014;29 Suppl 1:i54–i62. 10.1093/ndt/gft342
    1. Roos C, Wicovsky A, Muller N, Salzmann S, Rosenthal T, Kalthoff H, et al. Soluble and transmembrane TNF-like weak inducer of apoptosis differentially activate the classical and noncanonical NF-kappa B pathway. Journal of immunology. 2010;185(3):1593–605. 10.4049/jimmunol.0903555 .
    1. Wiley SR, Winkles JA. TWEAK, a member of the TNF superfamily, is a multifunctional cytokine that binds the TweakR/Fn14 receptor. Cytokine & growth factor reviews. 2003;14(3–4):241–9. .
    1. Brown SA, Ghosh A, Winkles JA. Full-length, membrane-anchored TWEAK can function as a juxtacrine signaling molecule and activate the NF-kappaB pathway. The Journal of biological chemistry. 2010;285(23):17432–41. 10.1074/jbc.M110.131979
    1. Nakayama M, Kayagaki N, Yamaguchi N, Okumura K, Yagita H. Involvement of TWEAK in interferon gamma-stimulated monocyte cytotoxicity. The Journal of experimental medicine. 2000;192(9):1373–80.
    1. Kaplan MJ, Lewis EE, Shelden EA, Somers E, Pavlic R, McCune WJ, et al. The apoptotic ligands TRAIL, TWEAK, and Fas ligand mediate monocyte death induced by autologous lupus T cells. Journal of immunology. 2002;169(10):6020–9. .
    1. Kim SH, Kang YJ, Kim WJ, Woo DK, Lee Y, Kim DI, et al. TWEAK can induce pro-inflammatory cytokines and matrix metalloproteinase-9 in macrophages. Circulation journal: official journal of the Japanese Circulation Society. 2004;68(4):396–9. .
    1. Campbell S, Burkly LC, Gao HX, Berman JW, Su L, Browning B, et al. Proinflammatory effects of TWEAK/Fn14 interactions in glomerular mesangial cells. Journal of immunology. 2006;176(3):1889–98. .
    1. Salzmann S, Seher A, Trebing J, Weisenberger D, Rosenthal A, Siegmund D, et al. Fibroblast growth factor inducible (Fn14)-specific antibodies concomitantly display signaling pathway-specific agonistic and antagonistic activity. The Journal of biological chemistry. 2013;288(19):13455–66. 10.1074/jbc.M112.435917
    1. Meighan-Mantha RL, Hsu DK, Guo Y, Brown SA, Feng SL, Peifley KA, et al. The mitogen-inducible Fn14 gene encodes a type I transmembrane protein that modulates fibroblast adhesion and migration. The Journal of biological chemistry. 1999;274(46):33166–76. .
    1. Feng SL, Guo Y, Factor VM, Thorgeirsson SS, Bell DW, Testa JR, et al. The Fn14 immediate-early response gene is induced during liver regeneration and highly expressed in both human and murine hepatocellular carcinomas. The American journal of pathology. 2000;156(4):1253–61. 10.1016/S0002-9440(10)64996-6
    1. Brown SA, Hanscom HN, Vu H, Brew SA, Winkles JA. TWEAK binding to the Fn14 cysteine-rich domain depends on charged residues located in both the A1 and D2 modules. The Biochemical journal. 2006;397(2):297–304. 10.1042/BJ20051362
    1. Brown SA, Richards CM, Hanscom HN, Feng SL, Winkles JA. The Fn14 cytoplasmic tail binds tumour-necrosis-factor-receptor-associated factors 1, 2, 3 and 5 and mediates nuclear factor-kappaB activation. The Biochemical journal. 2003;371(Pt 2):395–403. 10.1042/BJ20021730
    1. Han S, Yoon K, Lee K, Kim K, Jang H, Lee NK, et al. TNF-related weak inducer of apoptosis receptor, a TNF receptor superfamily member, activates NF-kappa B through TNF receptor-associated factors. Biochem Biophys Res Commun. 2003;305(4):789–96. .
    1. Bover LC, Cardo-Vila M, Kuniyasu A, Sun J, Rangel R, Takeya M, et al. A previously unrecognized protein-protein interaction between TWEAK and CD163: potential biological implications. Journal of immunology. 2007;178(12):8183–94. .
    1. Moreno JA, Munoz-Garcia B, Martin-Ventura JL, Madrigal-Matute J, Orbe J, Paramo JA, et al. The CD163-expressing macrophages recognize and internalize TWEAK: potential consequences in atherosclerosis. Atherosclerosis. 2009;207(1):103–10. 10.1016/j.atherosclerosis.2009.04.033 .
    1. Moller HJ, Nielsen MJ, Maniecki MB, Madsen M, Moestrup SK. Soluble macrophage-derived CD163: a homogenous ectodomain protein with a dissociable haptoglobin-hemoglobin binding. Immunobiology. 2010;215(5):406–12. 10.1016/j.imbio.2009.05.003 .
    1. Fick A, Lang I, Schafer V, Seher A, Trebing J, Weisenberger D, et al. Studies of binding of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) to fibroblast growth factor inducible 14 (Fn14). The Journal of biological chemistry. 2012;287(1):484–95. 10.1074/jbc.M111.287656
    1. Burkly LC. TWEAK/Fn14 axis: the current paradigm of tissue injury-inducible function in the midst of complexities. Semin Immunol. 2014;26(3):229–36. 10.1016/j.smim.2014.02.006 .
    1. Michaelson JS, Wisniacki N, Burkly LC, Putterman C. Role of TWEAK in lupus nephritis: a bench-to-bedside review. Journal of autoimmunity. 2012;39(3):130–42. 10.1016/j.jaut.2012.05.003
    1. Poveda J, Tabara LC, Fernandez-Fernandez B, Martin-Cleary C, Sanz AB, Selgas R, et al. TWEAK/Fn14 and Non-Canonical NF-kappaB Signaling in Kidney Disease. Frontiers in immunology. 2013;4:447 10.3389/fimmu.2013.00447
    1. Burkly LC, Michaelson JS, Zheng TS. TWEAK/Fn14 pathway: an immunological switch for shaping tissue responses. Immunol Rev. 2011;244(1):99–114. 10.1111/j.1600-065X.2011.01054.x .
    1. Campbell S, Michaelson J, Burkly L, Putterman C. The role of TWEAK/Fn14 in the pathogenesis of inflammation and systemic autoimmunity. Frontiers in bioscience: a journal and virtual library. 2004;9:2273–84. .
    1. Dohi T, Burkly LC. The TWEAK/Fn14 pathway as an aggravating and perpetuating factor in inflammatory diseases: focus on inflammatory bowel diseases. Journal of leukocyte biology. 2012;92(2):265–79. 10.1189/jlb.0112042 .
    1. Tran NL, McDonough WS, Donohue PJ, Winkles JA, Berens TJ, Ross KR, et al. The human Fn14 receptor gene is up-regulated in migrating glioma cells in vitro and overexpressed in advanced glial tumors. The American journal of pathology. 2003;162(4):1313–21. 10.1016/S0002-9440(10)63927-2
    1. Akahori H, Karmali V, Polavarapu R, Lyle AN, Weiss D, Shin E, et al. CD163 interacts with TWEAK to regulate tissue regeneration after ischaemic injury. Nat Commun. 2015;6 10.1038/ncomms8792
    1. Schneider P, Schwenzer R, Haas E, Muhlenbeck F, Schubert G, Scheurich P, et al. TWEAK can induce cell death via endogenous TNF and TNF receptor 1. European journal of immunology. 1999;29(6):1785–92. 10.1002/(SICI)1521-4141(199906)29:06<1785::AID-IMMU1785>;2-U .
    1. Nakayama M, Ishidoh K, Kayagaki N, Kojima Y, Yamaguchi N, Nakano H, et al. Multiple pathways of TWEAK-induced cell death. Journal of immunology. 2002;168(2):734–43. .
    1. Sanz AB, Justo P, Sanchez-Nino MD, Blanco-Colio LM, Winkles JA, Kreztler M, et al. The cytokine TWEAK modulates renal tubulointerstitial inflammation. Journal of the American Society of Nephrology: JASN. 2008;19(4):695–703. 10.1681/ASN.2007050577
    1. Xia Y, Herlitz LC, Gindea S, Wen J, Pawar RD, Misharin A, et al. Deficiency of fibroblast growth factor-inducible 14 (Fn14) preserves the filtration barrier and ameliorates lupus nephritis. Journal of the American Society of Nephrology: JASN. 2015;26(5):1053–70. 10.1681/ASN.2014030233
    1. Tajrishi MM, Zheng TS, Burkly LC, Kumar A. The TWEAK-Fn14 pathway: a potent regulator of skeletal muscle biology in health and disease. Cytokine & growth factor reviews. 2014;25(2):215–25. 10.1016/j.cytogfr.2013.12.004
    1. Novoyatleva T, Sajjad A, Engel FB. TWEAK-Fn14 Cytokine-Receptor Axis: A New Player of Myocardial Remodeling and Cardiac Failure. Frontiers in immunology. 2014;5:50 10.3389/fimmu.2014.00050
    1. Yepes M. TWEAK and the central nervous system. Mol Neurobiol. 2007;35(3):255–65. .
    1. Tirnitz-Parker JE, Viebahn CS, Jakubowski A, Klopcic BR, Olynyk JK, Yeoh GC, et al. Tumor necrosis factor-like weak inducer of apoptosis is a mitogen for liver progenitor cells. Hepatology. 2010;52(1):291–302. 10.1002/hep.23663 .
    1. Yoriki R, Akashi S, Sho M, Nomi T, Yamato I, Hotta K, et al. Therapeutic potential of the TWEAK/Fn14 pathway in intractable gastrointestinal cancer. Exp Ther Med. 2011;2(1):103–8. 10.3892/etm.2010.181
    1. Son A, Oshio T, Kawamura YI, Hagiwara T, Yamazaki M, Inagaki-Ohara K, et al. TWEAK/Fn14 pathway promotes a T helper 2-type chronic colitis with fibrosis in mice. Mucosal Immunol. 2013;6(6):1131–42. 10.1038/mi.2013.10 .
    1. Karaca G, Xie G, Moylan C, Swiderska-Syn M, Guy CD, Kruger L, et al. Role of Fn14 in acute alcoholic steatohepatitis in mice. Am J Physiol Gastrointest Liver Physiol. 2015;308(4):G325–34. 10.1152/ajpgi.00429.2013
    1. Wen J, Doerner J, Weidenheim K, Xia Y, Stock A, Michaelson JS, et al. TNF-like weak inducer of apoptosis promotes blood brain barrier disruption and increases neuronal cell death in MRL/lpr mice. Journal of autoimmunity. 2015;60:40–50. 10.1016/j.jaut.2015.03.005
    1. Ren MY, Sui SJ. The role of TWEAK/Fn14 in cardiac remodeling. Molecular biology reports. 2012;39(11):9971–7. 10.1007/s11033-012-1867-6 .
    1. Novoyatleva T, Janssen W, Wietelmann A, Schermuly RT, Engel FB. TWEAK/Fn14 axis is a positive regulator of cardiac hypertrophy. Cytokine. 2013;64(1):43–5. 10.1016/j.cyto.2013.05.009 .
    1. Zheng TS, Burkly LC. No end in site: TWEAK/Fn14 activation and autoimmunity associated- end-organ pathologies. Journal of leukocyte biology. 2008;84(2):338–47. 10.1189/jlb.0308165 .
    1. Izumi Y, Yabe D, Taniguchi A, Fukushima M, Nakai Y, Hosokawa M, et al. Circulating TNF receptor 2 is associated with the development of chronic kidney disease in non-obese Japanese patients with type 2 diabetes. Diabetes Res Clin Pract. 2013;99(2):145–50. 10.1016/j.diabres.2012.11.002 .
    1. Neirynck N, Glorieux G, Schepers E, Verbeke F, Vanholder R. Soluble tumor necrosis factor receptor 1 and 2 predict outcomes in advanced chronic kidney disease: a prospective cohort study. PloS one. 2015;10(3):e0122073 10.1371/journal.pone.0122073
    1. Xanthoulea S, Pasparakis M, Kousteni S, Brakebusch C, Wallach D, Bauer J, et al. Tumor necrosis factor (TNF) receptor shedding controls thresholds of innate immune activation that balance opposing TNF functions in infectious and inflammatory diseases. The Journal of experimental medicine. 2004;200(3):367–76. 10.1084/jem.20040435
    1. Hotta K, Sho M, Yamato I, Shimada K, Harada H, Akahori T, et al. Direct targeting of fibroblast growth factor-inducible 14 protein protects against renal ischemia reperfusion injury. Kidney international. 2011;79(2):179–88. 10.1038/ki.2010.379 .
    1. Tofovic SP, Kusaka H, Kost CK Jr., Bastacky S. Renal function and structure in diabetic, hypertensive, obese ZDFxSHHF-hybrid rats. Renal failure. 2000;22(4):387–406. .
    1. Tam FW, Riser BL, Meeran K, Rambow J, Pusey CD, Frankel AH. Urinary monocyte chemoattractant protein-1 (MCP-1) and connective tissue growth factor (CCN2) as prognostic markers for progression of diabetic nephropathy. Cytokine. 2009;47(1):37–42. 10.1016/j.cyto.2009.04.001 .
    1. Xuejing Z, Jiazhen T, Jun L, Xiangqing X, Shuguang Y, Fuyou L. Urinary TWEAK level as a marker of lupus nephritis activity in 46 cases. Journal of biomedicine & biotechnology. 2012;2012:359647 10.1155/2012/359647
    1. Pinckard JK, Sheehan KC, Arthur CD, Schreiber RD. Constitutive shedding of both p55 and p75 murine TNF receptors in vivo. Journal of immunology. 1997;158(8):3869–73. .
    1. Diez-Ruiz A, Tilz GP, Zangerle R, Baier-Bitterlich G, Wachter H, Fuchs D. Soluble receptors for tumour necrosis factor in clinical laboratory diagnosis. European journal of haematology. 1995;54(1):1–8. .
    1. Lantz M, Malik S, Slevin ML, Olsson I. Infusion of tumor necrosis factor (TNF) causes an increase in circulating TNF-binding protein in humans. Cytokine. 1990;2(6):402–6. .
    1. Jansen J, van der Poll T, Levi M, ten Cate H, Gallati H, ten Cate JW, et al. Inhibition of the release of soluble tumor necrosis factor receptors in experimental endotoxemia by an anti-tumor necrosis factor-alpha antibody. Journal of clinical immunology. 1995;15(1):45–50. .
    1. Lantz M, Gullberg U, Nilsson E, Olsson I. Characterization in vitro of a human tumor necrosis factor-binding protein. A soluble form of a tumor necrosis factor receptor. The Journal of clinical investigation. 1990;86(5):1396–402. 10.1172/JCI114853
    1. Leeuwenberg JF, Dentener MA, Buurman WA. Lipopolysaccharide LPS-mediated soluble TNF receptor release and TNF receptor expression by monocytes. Role of CD14, LPS binding protein, and bactericidal/permeability-increasing protein. Journal of immunology. 1994;152(10):5070–6. .
    1. Leeuwenberg JF, Jeunhomme TM, Buurman WA. Slow release of soluble TNF receptors by monocytes in vitro. Journal of immunology. 1994;152(8):4036–43. .
    1. Porteu F, Brockhaus M, Wallach D, Engelmann H, Nathan CF. Human neutrophil elastase releases a ligand-binding fragment from the 75-kDa tumor necrosis factor (TNF) receptor. Comparison with the proteolytic activity responsible for shedding of TNF receptors from stimulated neutrophils. The Journal of biological chemistry. 1991;266(28):18846–53. .
    1. Niewczas MA, Gohda T, Skupien J, Smiles AM, Walker WH, Rosetti F, et al. Circulating TNF receptors 1 and 2 predict ESRD in type 2 diabetes. Journal of the American Society of Nephrology: JASN. 2012;23(3):507–15. 10.1681/ASN.2011060627
    1. Gohda T, Niewczas MA, Ficociello LH, Walker WH, Skupien J, Rosetti F, et al. Circulating TNF receptors 1 and 2 predict stage 3 CKD in type 1 diabetes. Journal of the American Society of Nephrology: JASN. 2012;23(3):516–24. 10.1681/ASN.2011060628
    1. Aderka D. The potential biological and clinical significance of the soluble tumor necrosis factor receptors. Cytokine & growth factor reviews. 1996;7(3):231–40. .
    1. Llaurado G, Gonzalez-Clemente JM, Maymo-Masip E, Subias D, Vendrell J, Chacon MR. Serum levels of TWEAK and scavenger receptor CD163 in type 1 diabetes mellitus: relationship with cardiovascular risk factors. a case-control study. PloS one. 2012;7(8):e43919 10.1371/journal.pone.0043919

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