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Cited by 36Atherosclerosis and Cardiovascular DiseasesCholesterol and Lipid MetabolismLipoproteins and Cardiovascular Health

Atheroprotective Effects of Tumor Necrosis Factor-Stimulated Gene-6

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Watanabe, Rena, Watanabe, Hitomi, Takahashi, Yui, Kojima, Miho, Konii, Hanae, Watanabe, Kaho, Shirai, Remina, Sato, Kengo +7 more·2016·JACC: Basic to Translational Science
DOI 10.1016/j.jacbts.2016.07.008PMC PMC6113406
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Abstract

Tumor necrosis factor-stimulated gene-6 (TSG-6), an anti-inflammatory protein, was shown to be localized in the neointima of injury-induced rat arteries. However, the modulatory effect of TSG-6 on atherogenesis has not yet been reported. We aimed to evaluate the atheroprotective effects of TSG-6 on human endothelial cells (HECs), human monocyte-derived macrophages (HMDMs), human aortic smooth muscle cells (HASMCs) in vitro, and aortic lesions in apolipoprotein E-deficient mice, along with expression levels of TSG-6 in coronary lesions and plasma from patients with coronary artery disease (CAD). TSG-6 was abundantly expressed in HECs, HMDMs, and HASMCs in vitro. TSG-6 significantly suppressed cell proliferation and lipopolysaccharide-induced up-regulation of monocyte chemotactic protein-1, intercellular adhesion molecule-1, and vascular adhesion molecule-1 in HECs. TSG-6 significantly suppressed inflammatory M1 phenotype and suppressed oxidized low-density lipoprotein-induced foam cell formation associated with down-regulation of CD36 and acyl-CoA:cholesterol acyltransferase-1 in HMDMs. In HASMCs, TSG-6 significantly suppressed migration and proliferation, but increased collagen-1 and -3 expressions. Four-week infusion of TSG-6 into apolipoprotein E-deficient mice significantly retarded the development of aortic atherosclerotic lesions with decreased vascular inflammation, monocyte/macrophage, and SMC contents and increased collagen fibers. In addition, it decreased peritoneal M1 macrophages with down-regulation of inflammatory molecules and lowered plasma total cholesterol levels. In patients with CAD, plasma TSG-6 levels were significantly increased, and TSG-6 was highly expressed in the fibrous cap within coronary atherosclerotic plaques. These results suggest that TSG-6 contributes to the prevention and stability of atherosclerotic plaques. Thus, TSG-6 may serve as a novel therapeutic target for CAD.

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  1. [1]Milner C.M. Day A.J. TSG-6: a multifunctional protein associated with inflammation J Cell Sci 116 2003 1863 1873 12692188
  2. [2]Bardos T. Kamath R.V. Mikecz K. Glant T.T. Anti-inflammatory and chondroprotective effect of TGF-6 (tumor necrosis factor-α stimulated gene-6) in murine models of experimental arthritis Am J Pathol 159 2001 1711 1721 11696432 PMC1867074
  3. [3]Lee R.H. Pulin A.A. Seo M.J. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6 Cell Stem Cell 5 2009 54 63 19570514 PMC4154377
  4. [4]Lin Q.M. Zhao S. Zhou L.L. Fang X.S. Fu Y. Huang Z.T. Mesenchymal stem cells transplantation suppresses inflammatory responses in global cerebral ischemia: contribution of TNF-α-induced protein 6 Acta Pharmacol Sin 34 2013 784 792 23474707 PMC4002889
  5. [5]Wisniewski H.G. Maier R. Lotz M. TSG-6: a TNF-, IL-1-, and LPS-inducible secreted glycoprotein associated with arthritis J Immunol 151 1993 6593 6601 8245487
  6. [6]Fujimoto T. Savani R.C. Watari M. Day A.J. Strauss J.F. 3rd Induction of the hyaluronic acid-binding protein, tumor necrosis factor-stimulated gene-6, in cervical smooth muscle cells by tumor necrosis factor-α and prostaglandin E2 Am J Pathol 160 2002 1495 1502 11943733 PMC1867199
  7. [7]Lee T.H. Wisniewski H.G. Vilcek J. A novel secretory tumor necrosis factor-inducible protein (TSG-6) is a member of the family of hyaluronate binding proteins, closely related to the adhesion receptor CD44 J Cell Biol 116 1992 545 557 1730767 PMC2289279
  8. [8]Cao T.V. La M. Getting S.J. Day A.J. Perretti M. Inhibitory effects of TSG-6 link module on leukocyte-endothelial cell interactions in vitro and in vivo Microcirculation 11 2004 615 624 15513871
  9. [9]Dyer D.P. Thomson J.M. Hermant A. TSG-6 inhibits neutrophil migration via direct interaction with the chemokine CXCL8 J Immunol 192 2014 2177 2185 24501198 PMC3988464
  10. [10]Mindrescu C. Le J. Wisniewski H.G. Vilcek J. Up-regulation of cyclooxygenase-2 expression by TSG-6 protein in macrophage cell line Biochem Biophys Res Commun 330 2005 737 745 15809059
  11. [11]Choi H. Lee R.H. Bazhanov N. Oh J.Y. Prockop D.J. Anti-inflammatory protein TSG-6 secreted by activated MSCs attenuates zymosan-induced mouse peritonitis by decreasing TLR2/NF-κB signaling in resident macrophages Blood 118 2011 330 338 21551236 PMC3138686
  12. [12]Ye L. Mora R. Akhayani N. Haudenschild C.C. Liau G. Growth factor and cytokine-regulated hyaluronan-binding protein TSG-6 is localized to the injury-induced rat neointima and confers enhanced growth in vascular smooth muscle cells Circ Res 81 1997 289 296 9285629
  13. [13]Wang S.S. Hu S.W. Zhang Q.H. Xia A.X. Jiang Z.X. Chen X.M. Mesenchymal stem cells stabilize atherosclerotic vulnerable plaque by anti-inflammatory properties PLOS ONE 10 2015 e0136026 26288013 PMC4546153
  14. [14]Ross R. Agius L. The process of atherogenesis–cellular and molecular interaction: from experimental animal models to humans Diabetologia 35 Suppl 2 1992 S34 S40 1478376
  15. [15]Tabas I. Bornfeldt K.E. Macrophage phenotype and function in different stages of atherosclerosis Circ Res 118 2016 653 667 26892964 PMC4762068
  16. [16]Tiwari R.L. Singh V. Barthwal M.K. Macrophages: an elusive yet emerging therapeutic target of atherosclerosis Med Res Rev 28 2008 483 544 18000963
  17. [17]Watanabe T. Suguro T. Kanome T. Human urotensin II accelerates foam cell formation in human monocyte-derived macrophages Hypertension 46 2005 738 744 16172428
  18. [18]Obikane H. Abiko Y. Ueno H. Kusumi Y. Esumi M. Mitsumata M. Effect of endothelial cell proliferation on atherogenesis: a role of p21Sdi/Cip/Waf1 in monocyte adhesion to endothelial cells Atherosclerosis 212 2010 116 122 20598695
  19. [19]Watanabe K. Watanabe R. Konii H. Counteractive effects of omentin-1 against atherogenesis Cardiovasc Res 110 2016 118 128 26790473
  20. [20]Watanabe T. Nishio K. Kanome T. Impact of salusin-α and -β on human macrophage foam cell formation and coronary atherosclerosis Circulation 117 2008 638 648 18212280
  21. [21]Xu G. Watanabe T. Iso Y. Preventive effects of heregulin-β1 on macrophage foam cell formation and atherosclerosis Circ Res 105 2009 500 510 19644050
  22. [22]Konii H. Sato K. Kikuchi S. Stimulatory effects of cardiotrophin 1 on atherosclerosis Hypertension 62 2013 942 950 24041953
  23. [23]Hasegawa A. Sato K. Shirai R. Vasoprotective effects of urocortin 1 against atherosclerosis in vitro and in vivo PLOS ONE 9 2014 e110866 25462164 PMC4251828
  24. [24]Yamamoto K. Tajima Y. Hasegawa A. Contrasting effects of stanniocalcin-related polypeptides on macrophage foam cell formation and vascular smooth muscle cell migration Peptides 82 2016 120 127 27346255
  25. [25]Naito C. Hashimoto M. Watanabe K. Facilitatory effects of fetuin-A on atherosclerosis Atherosclerosis 246 2016 344 351 26828753
  26. [26]Watanabe J. Shetty A.K. Hattiangady B. Administration of TSG-6 improves memory after traumatic brain injury in mice Neurobiol Dis 59C 2013 86 99 PMC3790317 23851308
  27. [27]Nagashima M. Watanabe T. Terasaki M. Native incretins prevent the development of atherosclerotic lesions in apolipoprotein E knockout mice Diabetologia 54 2011 2649 2659 21786155 PMC3168747
  28. [28]Forteza R. Casalino-Matsuda S.M. Monzon M.E. TSG-6 potentiates the antitissue kallikrein activity of inter-α-inhibitor through bikunin release Am J Respir Cell Mol Biol 36 2007 20 31 16873769 PMC1899306
  29. [29]Lee T.H. Wisniewski H.G. Klampfer L. Oppenheim J.D. Vilcek J. TSG-6: a novel secretory protein inducible by tumor necrosis factor or interleukin-1 in fibroblasts and mononuclear cells Fiers W. Buurman W.A. Tumor Necrosis Factor: Molecular and Cellular Biology and Clinical Relevance 1993 Karger Basel 90 95
  30. [30]Tuo J. Cao X. Shen D. Anti-inflammatory recombinant TSG-6 stabilizes the progression of focal retinal degeneration in a murine model J Neuroinflammation 9 2012 59 22452753 PMC3359240
  31. [31]Oh J.Y. Roddy G.W. Choi H. Anti-inflammatory protein TSG-6 reduces inflammatory damage to the cornea following chemical and mechanical injury Proc Natl Acad Sci U S A 107 2010 16875 16880 20837529 PMC2947923
  32. [32]Lauer M.E. Cheng G. Swaidani S. Aronica M.A. Weigel P.H. Hascall V.C. Tumor necrosis factor-stimulated gene-6 (TSG-6) amplifies hyaluronan synthesis by airway smooth muscle cells J Biol Chem 288 2013 423 431 23129777 PMC3537040
  33. [33]Guo P. Zhang S.Z. He H. Zhu Y.T. Tseng S.C. TSG-6 controls transcription and activation of matrix metalloproteinase 1 in conjunctivochalasis Invest Ophthalmol Vis Sci 53 2012 1372 1380 22297496 PMC3339910
  34. [34]Mahoney D.J. Mulloy B. Forster M.J. Characterization of the interaction between tumor necrosis factor-stimulated gene-6 and heparin: implications for the inhibition of plasmin in extracellular matrix microenvironments J Biol Chem 280 2005 27044 27055 15917224
  35. [35]Mindrescu C. Thorbecke G.J. Klein M.J. Vilcek J. Wisniewski H.G. Amelioration of collagen-induced arthritis in DBA/1J mice by recombinant TSG-6, a tumor necrosis factor/interleukin-1-inducible protein Arthritis Rheum 43 2000 2668 2677 11145024
  36. [36]Szántó S. Bárdos T. Gál I. Glant T.T. Mikecz K. Enhanced neutrophil extravasation and rapid progression of proteoglycan-induced arthritis in TSG-6-knockout mice Arthritis Rheum 50 2004 3012 3022 15457471
  37. [37]Mindrescu C. Dias A.A. Olszewski R.J. Klein M.J. Reis L.F. Wisniewski H.G. Reduced susceptibility to collagen-induced arthritis in DBA/1J mice expressing the TSG-6 transgene Arthritis Rheum 46 2002 2453 2464 12355494
  38. [38]De Paoli F. Staels B. Chinetti-Gbaguidi G. Macrophage phenotypes and their modulation in atherosclerosis Circ J 78 2014 1775 1781 24998279
  39. [39]Leosco D. Fineschi M. Pierli C. Intracoronary serotonin release after high-pressure coronary stenting Am J Cardiol 84 1999 1317 1322 10614797
  40. [40]Schuijt M.P. van Kats J.P. de Zeeuw S. Cardiac interstitial fluid levels of angiotensin I and II in the pig J Hypertens 17 1999 1885 1891 10703885

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Authors
Watanabe, R., Watanabe, H., Takahashi, Y., Kojima, M., Konii, H., Watanabe, K., Shirai, R., Sato, K., Matsuyama, T.-A., Ishibashi-Ueda, H., Iso, Y., Koba, S., Kobayashi, Y., Hirano, T., & Watanabe, T.
Affiliations
  • Tokyo University of Pharmacy and Life Sciences (JP)
  • National Cerebral and Cardiovascular Center (JP)
  • SHOWA Medical University (JP)
Corresponding author
Watanabe, Takuya
ORCID
Venue
JACC: Basic to Translational Science
Publisher
Elsevier BV
Published
2016-10
Volume
1
Issue
6
Pages
494-509
ISSN
2452-302X (ISSN-L)
DOI
10.1016/j.jacbts.2016.07.008
PMC
PMC6113406
OpenAlex
W2546230218
Cited by
36
References
0
Citations by year
2025: 2 · 2024: 1 · 2023: 4 · 2022: 5 · 2021: 6 · 2020: 3 · 2019: 3 · 2018: 11 · 2017: 1
FWCI
3.03
Type
journal article
Language
en
Open access
Licence
Locations
  • JACC Basic to Translational Science (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Japan Society for the Promotion of Science
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
TSG-6, atheroprotection, atherosclerosis, coronary artery disease, atherosclerotic plaque stability, foam cell formation, M1 macrophage polarization, vascular inflammation, endothelial cells, smooth muscle cells, ApoE-deficient mice, fibrous cap, anti-inflammatory therapy

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