Genomes and Genes
tumor necrosis factors
Summary: A family of proteins that were originally identified by their ability to cause NECROSIS of NEOPLASMS. Their necrotic effect on cells is mediated through TUMOR NECROSIS FACTOR RECEPTORS which induce APOPTOSIS.
- Wiens G, Glenney G. Origin and evolution of TNF and TNF receptor superfamilies. Dev Comp Immunol. 2011;35:1324-35 pubmed publisher..The increasing interest and use of TNFSF and TNFRSF modulators in human and animal medicine underscores the need to understand the evolutionary origins as well as conserved and novel functions of these biologically important molecules. ..
- Yilmaz M, Sonmez A, Ortiz A, Saglam M, Kilic S, Eyileten T, et al. Soluble TWEAK and PTX3 in nondialysis CKD patients: impact on endothelial dysfunction and cardiovascular outcomes. Clin J Am Soc Nephrol. 2011;6:785-92 pubmed publisher..Now, we hypothesize that both sTWEAK and PTX3 act as biomarkers of cardiovascular outcomes in nondialysis CKD patients...
- Haile W, Echeverry R, Wu F, Guzman J, An J, Wu J, et al. Tumor necrosis factor-like weak inducer of apoptosis and fibroblast growth factor-inducible 14 mediate cerebral ischemia-induced poly(ADP-ribose) polymerase-1 activation and neuronal death. Neuroscience. 2010;171:1256-64 pubmed publisher..This is a novel pathway for hypoxia/ischemia-induced TWEAK-mediated cell death and a potential therapeutic target for ischemic stroke. ..
- Richter B, Rychli K, Hohensinner P, Berger R, Mörtl D, Neuhold S, et al. Differences in the predictive value of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in advanced ischemic and non-ischemic heart failure. Atherosclerosis. 2010;213:545-8 pubmed publisher..sTWEAK-induced proliferation of cardiomyocytes may explain its impact on suvival. The different prognostic value of sTWEAK in ischemic and non-ischemic HF may point towards distinct pathogenic pathways determining the course of disease. ..
- Nocentini G, Ronchetti S, Petrillo M, Riccardi C. Pharmacological modulation of GITRL/GITR system: therapeutic perspectives. Br J Pharmacol. 2012;165:2089-99 pubmed publisher..However, differences between mouse and human GITRL/GITR systems suggest that further preclinical studies are needed to better understand how safe therapeutic results can be obtained and to design appropriate clinical trials. ..
- Yilmaz M, Carrero J, Martin Ventura J, Sonmez A, Saglam M, Celik T, et al. Combined therapy with renin-angiotensin system and calcium channel blockers in type 2 diabetic hypertensive patients with proteinuria: effects on soluble TWEAK, PTX3, and flow-mediated dilation. Clin J Am Soc Nephrol. 2010;5:1174-81 pubmed publisher..Two surrogate biomarkers of endothelial function are therefore identified with potential as therapeutic targets. The study was registered in clinicaltrials.gov as NCT00921570. ..
- Echeverry R, Wu F, Haile W, Wu J, Yepes M. The cytokine tumor necrosis factor-like weak inducer of apoptosis and its receptor fibroblast growth factor-inducible 14 have a neuroprotective effect in the central nervous system. J Neuroinflammation. 2012;9:45 pubmed publisher..These data indicate that TWEAK may be a potential therapeutic strategy to protect the brain from the devastating effects of an ischemic injury. ..
- Pelekanou V, Notas G, Theodoropoulou K, Kampa M, Takos D, Alexaki V, et al. Detection of the TNFSF members BAFF, APRIL, TWEAK and their receptors in normal kidney and renal cell carcinomas. Anal Cell Pathol (Amst). 2011;34:49-60 pubmed publisher..This is the first study, presenting together the TNFSF members APRIL, BAFF, TWEAK and their receptors in different areas of normal renal tissue and RCC, suggesting a potential role of these TNFSF members in renal tumor biology. ..
- Paul P, Gupta S, Bhatnagar S, Panguluri S, Darnay B, Choi Y, et al. Targeted ablation of TRAF6 inhibits skeletal muscle wasting in mice. J Cell Biol. 2010;191:1395-411 pubmed publisher..This study unveils a novel mechanism of skeletal muscle atrophy and suggests that TRAF6 is an important therapeutic target to prevent skeletal muscle wasting. ..
- Chen H, Wang D, Ren M, Wang Q, Sui S. TWEAK/Fn14 promotes the proliferation and collagen synthesis of rat cardiac fibroblasts via the NF-?B pathway. Mol Biol Rep. 2012;39:8231-41 pubmed publisher..The present study suggested that the TWEAK/Fn14 axis increased cell proliferation and collagen synthesis by activating the NF-?B pathway and increasing MMP-9 activity. This axis may be important for regulating myocardial fibrosis. ..
- Vendrell J, Maymó Masip E, Tinahones F, Garcia Espana A, Megia A, Caubet E, et al. Tumor necrosis-like weak inducer of apoptosis as a proinflammatory cytokine in human adipocyte cells: up-regulation in severe obesity is mediated by inflammation but not hypoxia. J Clin Endocrinol Metab. 2010;95:2983-92 pubmed publisher..Our data suggest that TWEAK acts as a pro-inflammatory cytokine in the adipose tissue and that inflammation, but not hypoxia, may be behind its up-regulation in severe obesity. ..
- Munoz Garcia B, Madrigal Matute J, Moreno J, Martin Ventura J, Lopez Franco O, Sastre C, et al. TWEAK-Fn14 interaction enhances plasminogen activator inhibitor 1 and tissue factor expression in atherosclerotic plaques and in cultured vascular smooth muscle cells. Cardiovasc Res. 2011;89:225-33 pubmed publisher..our results indicate that the TWEAK-Fn14 axis can regulate activation of TF and PAI-1 expression in vascular cells. TWEAK-Fn14 may be a therapeutic target in the prothrombotic complications associated with atherosclerosis. ..
- Brown S, Ghosh A, Winkles J. Full-length, membrane-anchored TWEAK can function as a juxtacrine signaling molecule and activate the NF-kappaB pathway. J Biol Chem. 2010;285:17432-41 pubmed publisher..Thus, TWEAK can act in a juxtacrine manner to initiate cellular responses, and this property may be important for TWEAK function during physiological wound repair and disease pathogenesis. ..
- Kataria N, Bartold P, Dharmapatni A, Atkins G, Holding C, Haynes D. Expression of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor, fibroblast growth factor-inducible 14 protein (Fn14), in healthy tissues and in tissues affected by periodontitis. J Periodontal Res. 2010;45:564-73 pubmed publisher..The aim of the present study was to investigate the expression of TWEAK and Fn14 at the protein and mRNA levels in gingival biopsies from periodontitis patients and from clinically healthy patients...
- Schmid A, Kopp A, Hanses F, Bala M, Muller M, Schaffler A. The novel adipokine C1q/TNF-related protein-3 is expressed in human adipocytes and regulated by metabolic and infection-related parameters. Exp Clin Endocrinol Diabetes. 2012;120:611-7 pubmed publisher..CTRP-3 is expressed in human adipocytes and plays an important role in adipocyte physiology such as lipolysis and adipokine secretion. Both, metabolic factors and infection/inflammation-related factors regulate CTRP-3 expression. ..
- Zhou Z, Han V, Han J. New components of the necroptotic pathway. Protein Cell. 2012;3:811-7 pubmed publisher..Here we review the new members of this necroptosis pathway, MLKL, PGAM5, Drp1 and DAI, and discuss some of their possible applications according to recent findings...
- Kumar A, Bhatnagar S, Paul P. TWEAK and TRAF6 regulate skeletal muscle atrophy. Curr Opin Clin Nutr Metab Care. 2012;15:233-9 pubmed publisher..Recent findings have uncovered TWEAK and TRAF6 as novel regulators of skeletal muscle atrophy. These proteins should potentially be used as molecular targets for prevention and/or treatment of muscular atrophy in future therapies. ..
- Croft M, Duan W, Choi H, Eun S, Madireddi S, Mehta A. TNF superfamily in inflammatory disease: translating basic insights. Trends Immunol. 2012;33:144-52 pubmed publisher..Here, we examine recent data regarding the potential of these molecules as targets for therapy of autoimmune and inflammatory disease. ..
- Muller N, Schneider B, Pfizenmaier K, Wajant H. Superior serum half life of albumin tagged TNF ligands. Biochem Biophys Res Commun. 2010;396:793-9 pubmed publisher..In conclusion, our data suggest that genetic fusion to serum albumin is a powerful and generally applicable mean to improve bioavailability and in vivo activity of TNF ligands. ..
- Chen T, Guo Z, Li M, Li J, Jiao X, Zhang Y, et al. Tumour necrosis factor-like weak inducer of apoptosis (TWEAK), an important mediator of endothelial inflammation, is associated with the pathogenesis of Henoch-Schonlein purpura. Clin Exp Immunol. 2011;166:64-71 pubmed publisher..TWEAK may act as a regulator of nuclear factor-?B (NF-?B) activation and chemokine production in human dermal microvascular endothelial cells, thus promoting leucocyte migration in cutaneous vasculitis. ..
- Svestak M, Sporova L, Hejduk P, Lacnak B, Stejskal D. Collagenous repeat-containing sequence of 26 kDa protein - a newly discovered adipokine - sensu lato - A minireview. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2010;154:199-202 pubmed..The effect of recombinant CORS-26 on insulin signaling in the presence of the metabolic syndrome needs to be investigated to further evaluate the physiological and pathophysiological role of this protein. ..
- Choi K, Hwang S, Hong H, Yang S, Choi H, Yoo H, et al. C1q/TNF-related protein-3 (CTRP-3) and pigment epithelium-derived factor (PEDF) concentrations in patients with type 2 diabetes and metabolic syndrome. Diabetes. 2012;61:2932-6 pubmed publisher..Both CTRP-3 and PEDF concentrations were increased in subjects with metabolic syndrome and associated with various cardiometabolic risk factors. ..
- Michaelson J, Wisniacki N, Burkly L, Putterman C. Role of TWEAK in lupus nephritis: a bench-to-bedside review. J Autoimmun. 2012;39:130-42 pubmed publisher..Taken together, targeting the TWEAK/Fn14 axis represents a potential new therapeutic paradigm for achieving renal protection in LN patients...
- Fick A, Lang I, Schäfer 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). J Biol Chem. 2012;287:484-95 pubmed publisher..Thus, although ?25 activated TNFR1 trimers were sufficient to trigger half-maximal IL8 production, more than 2500 cell-bound oligomerized TWEAK trimers were required to elicit a similar response. ..
- Urbonaviciene G, Martin Ventura J, Lindholt J, Urbonavicius S, Moreno J, Egido J, et al. Impact of soluble TWEAK and CD163/TWEAK ratio on long-term cardiovascular mortality in patients with peripheral arterial disease. Atherosclerosis. 2011;219:892-9 pubmed publisher..72-0.86) vs. 0.84 (0.78-0.90), p = 0.019). Decreased sTWEAK concentration, and increased sCD163/sTWEAK ratio were significantly and independently associated with long-term cardiovascular mortality in patients with lower-extremity PAD. ..
- 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 Int. 2011;79:179-88 pubmed publisher..Thus, we conclude that Fn14 is a critical mediator in the pathogenesis of ischemia reperfusion injury. ..
- Lecour S, James R. When are pro-inflammatory cytokines SAFE in heart failure?. Eur Heart J. 2011;32:680-5 pubmed publisher..In this review, we will discuss whether targeting the SAFE pathway may be considered as a preventive and/or therapeutic measure for the treatment of heart failure. ..
- Chorianopoulos E, Jarr K, Steen H, Giannitsis E, Frey N, Katus H. Soluble TWEAK is markedly upregulated in patients with ST-elevation myocardial infarction and related to an adverse short-term outcome. Atherosclerosis. 2010;211:322-6 pubmed publisher..Further work is needed to precisely define the potential role of sTWEAK as a prognostic marker in myocardial infarction. ..
- Tirnitz Parker J, Viebahn C, Jakubowski A, Klopcic B, Olynyk J, Yeoh G, et al. Tumor necrosis factor-like weak inducer of apoptosis is a mitogen for liver progenitor cells. Hepatology. 2010;52:291-302 pubmed publisher..TWEAK acts directly and stimulates LPC mitosis in an Fn14-dependent and NFkappaB-dependent fashion, and signaling via this pathway mediates the LPC response to CDE-induced injury and regeneration. ..
- Wang C, Chen L, Pan H, Leng R, Qin W, Ye D. Expression of human tumor necrosis factor-like weak inducer of apoptosis in patients with systemic lupus erythematosus. Clin Rheumatol. 2012;31:335-9 pubmed publisher..In this study, patients with SLE express low levels of TWEAK mRNA but high levels of sTWEAK. Additionally, sTWEAK level was associated with several clinical manifestations of SLE, indicating that TWEAK may play a complex role in SLE. ..
- Burkly L, Michaelson J, Zheng T. TWEAK/Fn14 pathway: an immunological switch for shaping tissue responses. Immunol Rev. 2011;244:99-114 pubmed publisher..Whereas transient TWEAK/Fn14 activation promotes productive tissue responses after injury, excessive or persistent TWEAK/Fn14 activation drives pathological tissue responses, leading to progressive damage and degeneration. ..
- Bhatnagar S, Kumar A. The TWEAK-Fn14 system: breaking the silence of cytokine-induced skeletal muscle wasting. Curr Mol Med. 2012;12:3-13 pubmed
- Zimmermann M, Koreck A, Meyer N, Basinski T, Meiler F, Simone B, et al. TNF-like weak inducer of apoptosis (TWEAK) and TNF-? cooperate in the induction of keratinocyte apoptosis. J Allergy Clin Immunol. 2011;127:200-7, 207.e1-10 pubmed publisher..The high expression of TWEAK in lesional AD skin contributes to the difference in keratinocyte apoptosis and lesional formation between AD and psoriasis. ..
- Vanlangenakker N, Vanden Berghe T, Bogaert P, Laukens B, Zobel K, Deshayes K, et al. cIAP1 and TAK1 protect cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent reactive oxygen species production. Cell Death Differ. 2011;18:656-65 pubmed publisher..In conclusion, our data indicate that cIAP1 and TAK1 protect cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent ROS production. ..
- Gungor O, Kismali E, Sisman A, Kircelli F, Carrero J, Tatar E, et al. The relationships between serum sTWEAK, FGF-23 levels, and carotid atherosclerosis in renal transplant patients. Ren Fail. 2013;35:77-81 pubmed publisher..In adjusted models using linear regression analysis, only age and serum TWEAK levels were predictors for CA-IMT. There is a positive correlation between CA-IMT and sTWEAK, but not with FGF-23 levels in renal transplant patients. ..
- Enwere E, Holbrook J, Lejmi Mrad R, Vineham J, Timusk K, Sivaraj B, et al. TWEAK and cIAP1 regulate myoblast fusion through the noncanonical NF-?B signaling pathway. Sci Signal. 2012;5:ra75 pubmed publisher..These results identify roles for TWEAK, cIAP1, and noncanonical NF-?B signaling in the regulation of myoblast fusion and highlight a role for cytokine signaling during adult skeletal myogenesis...
- Peterson J, Wei Z, Wong G. C1q/TNF-related protein-3 (CTRP3), a novel adipokine that regulates hepatic glucose output. J Biol Chem. 2010;285:39691-701 pubmed publisher..This study provides the first functional evidence linking CTRP3 to hepatic glucose metabolism and establishes CTRP3 as a novel adipokine. ..
- Michaelson J, Amatucci A, Kelly R, Su L, Garber E, Day E, et al. Development of an Fn14 agonistic antibody as an anti-tumor agent. MAbs. 2011;3:362-75 pubmed..Taken together, the anti-tumor properties of BIIB036 validate Fn14 as a promising target in oncology and demonstrate its potential therapeutic utility in multiple solid tumor indications. ..
- Hofmann C, Chen N, Obermeier F, Paul G, Büchler C, Kopp A, et al. C1q/TNF-related protein-3 (CTRP-3) is secreted by visceral adipose tissue and exerts antiinflammatory and antifibrotic effects in primary human colonic fibroblasts. Inflamm Bowel Dis. 2011;17:2462-71 pubmed publisher..CTRP-3 exerts potent antiinflammatory and antifibrotic effects in CLPF by antagonizing the LPS pathway and by targeting the TGF-?-CTGF-collagen I pathway. ..
- Filusch A, Zelniker T, Baumgartner C, Eschricht S, Frey N, Katus H, et al. Soluble TWEAK predicts hemodynamic impairment and functional capacity in patients with pulmonary arterial hypertension. Clin Res Cardiol. 2011;100:879-85 pubmed publisher..Further prospective studies are needed to determine the role of sTWEAK as potential biomarker in patients with PAH. ..
- Mittal A, Bhatnagar S, Kumar A, Lach Trifilieff E, Wauters S, Li H, et al. The TWEAK-Fn14 system is a critical regulator of denervation-induced skeletal muscle atrophy in mice. J Cell Biol. 2010;188:833-49 pubmed publisher..This study reveals a novel mediator of skeletal muscle atrophy and indicates that the TWEAK-Fn14 system is an important target for preventing skeletal muscle wasting. ..
- Schaffler A, Buechler C. CTRP family: linking immunity to metabolism. Trends Endocrinol Metab. 2012;23:194-204 pubmed publisher..This review focuses on the biochemistry and pleiotropic physiological functions of CTRPs as new molecular mediators connecting inflammatory and metabolic diseases. ..
- Ikner A, Ashkenazi A. TWEAK induces apoptosis through a death-signaling complex comprising receptor-interacting protein 1 (RIP1), Fas-associated death domain (FADD), and caspase-8. J Biol Chem. 2011;286:21546-54 pubmed publisher..The proapoptotic activity of TWEAK is modulated by cIAP1 and CYLD and engages both the extrinsic and intrinsic signaling pathways. ..
- Zhu L, Zhang H, Mei Y, Zhao Y, Zhang Z. Role of tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) axis in rheumatic diseases. Chin Med J (Engl). 2012;125:3898-904 pubmed..This review discusses the role of the TWEAK-Fn14 axis in several rheumatic diseases and the potential therapeutic benefits of modulation of the TWEAK-Fn14 pathway...
- Kopp A, Bala M, Buechler C, Falk W, Gross P, Neumeier M, et al. C1q/TNF-related protein-3 represents a novel and endogenous lipopolysaccharide antagonist of the adipose tissue. Endocrinology. 2010;151:5267-78 pubmed publisher..CTRP-3 inhibits three basic and common proinflammatory pathways involved in obesity and type 2 diabetes mellitus (adipo-inflammation) by acting as an endogenous LPS antagonist of the adipose tissue. ..
- Stephan D, Sbai O, Wen J, Couraud P, Putterman C, Khrestchatisky M, et al. TWEAK/Fn14 pathway modulates properties of a human microvascular endothelial cell model of blood brain barrier. J Neuroinflammation. 2013;10:9 pubmed publisher..These results support the contention that the TWEAK/Fn14 pathway could contribute at least to the endothelial steps of neuroinflammation. ..
- Iyer C, Kosters A, Sethi G, Kunnumakkara A, Aggarwal B, Versalovic J. Probiotic Lactobacillus reuteri promotes TNF-induced apoptosis in human myeloid leukemia-derived cells by modulation of NF-kappaB and MAPK signalling. Cell Microbiol. 2008;10:1442-52 pubmed publisher..An improved understanding of L. reuteri-mediated effects on apoptotic signalling pathways may facilitate development of future probiotics-based regimens for prevention of colorectal cancer and inflammatory bowel disease...
- Kumar M, Makonchuk D, Li H, Mittal A, Kumar A. TNF-like weak inducer of apoptosis (TWEAK) activates proinflammatory signaling pathways and gene expression through the activation of TGF-beta-activated kinase 1. J Immunol. 2009;182:2439-48 pubmed publisher..Collectively, our study demonstrates that TAK1 and Akt are the important components of TWEAK-induced proinflammatory signaling and gene expression. ..