Thrombospondin 1 in Metabolic Diseases

Department of Biology, Wilkes University, Wilkes Barre, PA, United States,

Edited by: Hiu Yee Kwan, Hong Kong Baptist University, Hong Kong

Reviewed by: David Soto-Pantoja, Wake Forest School of Medicine, United States; David D. Roberts, National Institutes of Health (NIH), United States; Anthony L. Schwartz, Morphiex Biotherapeutics, United States; Bin Ren, University of Alabama at Birmingham, United States; Gabor Csanyi, Augusta University, United States

*Correspondence: Linda S. Gutierrez, ude.sekliw@zerreitug.adnil

This article was submitted to Cellular Endocrinology, a section of the journal Frontiers in Endocrinology

Edited by: Hiu Yee Kwan, Hong Kong Baptist University, Hong Kong

Received 2020 Dec 9; Accepted 2021 Mar 1.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Abstract

The thrombospondin family comprises of five multifunctional glycoproteins, whose best-studied member is thrombospondin 1 (TSP1). This matricellular protein is a potent antiangiogenic agent that inhibits endothelial migration and proliferation, and induces endothelial apoptosis. Studies have demonstrated a regulatory role of TSP1 in cell migration and in activation of the latent transforming growth factor beta 1 (TGFβ1). These functions of TSP1 translate into its broad modulation of immune processes. Further, imbalances in immune regulation have been increasingly linked to pathological conditions such as obesity and diabetes mellitus. While most studies in the past have focused on the role of TSP1 in cancer and inflammation, recently published data have revealed new insights about the role of TSP1 in physiological and metabolic disorders. Here, we highlight recent findings that associate TSP1 and its receptors to obesity, diabetes, and cardiovascular diseases. TSP1 regulates nitric oxide, activates latent TGFβ1, and interacts with receptors CD36 and CD47, to play an important role in cell metabolism. Thus, TSP1 and its major receptors may be considered a potential therapeutic target for metabolic diseases.

Keywords: cardiovascular disease, atherosclerosis, diabetes, angiogenesis, TGFβ1, obesity, nitric oxide

Abstract

Acknowledgments

We would like to thank Editage (www.editage.com) for English language editing.

Acknowledgments

References

1. Baenziger NL, Brodie GN, Majerus PW. A thrombin-sensitive protein of human plateletmembranes. Proc Natl Acad Sci USA (1971)68(1):240–3. 10.1073/pnas.68.1.240 ] [
2. Lawler J, Hynes RO. The structure of human thrombospondin, an adhesive glycoprotein withmultiple calcium-binding sites and homologies with several different proteins.J Cell Biol (1986)103(5):1635–48. 10.1083/jcb.103.5.1635 ] [
3. Taraboletti G, Roberts DD, Liotta LA. Thrombospondin-induced tumor cell migration: haptotaxis and chemotaxis are mediated by different molecular domains. J Cell Biol (1987) 105(5):2409–15. 10.1083/jcb.105.5.2409 ] [
4. Guo N, Krutzsch HC, Inman JK, Roberts DD. Thrombospondin 1 and type I repeat peptides of thrombospondin 1 specifically induce apoptosis of endothelial cells. Cancer Res (1997) 57(9):1735–42. [[PubMed]
5. Good DJ, Polverini PJ, Rastinejad F, Le Beau MM, Lemons RS, Frazier WA, et al. . A tumor suppressor-dependent inhibitor of angiogenesis is immunologically and functionally indistinguishable from a fragment of thrombospondin. Proc Natl Acad Sci USA (1990) 87(17):6624–8. 10.1073/pnas.87.17.6624 ] [
6. Jiménez B, Volpert OV, Crawford SE, Febbraio M, Silverstein RL, Bouck N. Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1. Nat Med (2000) 6(1):41–8. 10.1038/71517 [] [[PubMed]
7. Calzada MJ, Sipes JM, Krutzsch HC, Yurchenco PD, Annis DS, Mosher DF, et al. . Recognition of the N-terminal modules of thrombospondin-1 and thrombospondin-2 by alpha6beta1 integrin. J Biol Chem (2003) 278(42):40679–87. 10.1074/jbc.M302014200 [] [[PubMed]
8. Lopez-Dee Z, Pidcock K, Gutierrez LS. Thrombospondin-1: multiple paths to inflammation. Mediators Inflamm (2011) 2011:296069. 10.1155/2011/296069 ] [
9. Carlson CB, Lawler J, Mosher DF. Structures of thrombospondins. Cell Mol Life Sci (2008) 65(5):672–86. 10.1007/s00018-007-7484-1 ] [
10. Asch AS, Silbiger S, Heimer E, Nachman RL. Thrombospondin sequence motif (CSVTCG) is responsible for CD36 binding. Biochem Biophys Res Commun (1992) 182(3):1208–17. 10.1016/0006-291x(92)91860-s [] [[PubMed]
11. Silverstein RL, Febbraio M. CD36, a scavenger receptor involved in immunity, metabolism, angiogenesis, and behavior. Sci Signal (2009) 2(72):re3. 10.1126/scisignal.272re3 ] [
12. Crawford SE, Stellmach V, Murphy-Ullrich JE, Ribeiro SM, Lawler J, Hynes RO, et al. . Thrombospondin-1 is a major activator of TGF-beta1 in vivo. Cell (1998) 93(7):1159–70. 10.1016/s0092-8674(00)81460-9 [] [[PubMed]
13. Hogg PJ, Owensby DA, Mosher DF, Misenheimer TM, Chesterman CN. Thrombospondin is a tight-binding competitive inhibitor ofneutrophil elastase. J Biol Chem (1993)268(10):7139–46. 10.1016/S0021-9258(18)53157-4 [] [[PubMed]
14. Margosio B, Rusnati M, Bonezzi K, Cordes BL, Annis DS, Urbinati C, et al. . Fibroblast growth factor-2 binding to the thrombospondin-1 type III repeats, a novel antiangiogenic domain. Int J Biochem Cell Biol (2008) 40(4):700–9. 10.1016/j.biocel.2007.10.002 ] [
15. Isenberg JS, Martin-Manso G, Maxhimer JB, Roberts DD. Regulation of nitric oxide signalling by thrombospondin 1: implications for anti-angiogenic therapies. Nat Rev Cancer (2009) 9(3):182–94. 10.1038/nrc2561 ] [
16. Mumby SM, Raugi GJ, Bornstein P. Interactions of thrombospondin with extracellular matrix proteins: selective binding to type V collagen. J Cell Biol (1984) 98(2):646–52. 10.1083/jcb.98.2.646 ] [
17. Li Z, He L, Wilson K, Roberts D. Thrombospondin-1 inhibits TCR-mediated T lymphocyte early activation. J Immunol (2001) 166(4):2427–36. 10.4049/jimmunol.166.4.2427 [] [[PubMed]
18. Malek MH, Olfert IM. Global deletion of thrombospondin-1 increases cardiac and skeletal muscle capillarity and exercise capacity in mice. Exp Physiol (2009) 94(6):749–60. 10.1113/expphysiol.2008.045989 [] [[PubMed]
19. Gao JB, Tang WD, Wang HX, Xu Y. Predictive value of thrombospondin-1 for outcomes in patients with acute ischemic stroke. Clin Chim Acta (2015) 450:176–80. 10.1016/j.cca.2015.08.014 [] [[PubMed]
20. Choi KY, Kim DB, Kim MJ, Kwon BJ, Chang SY, Jang SW, et al. . Higher plasma thrombospondin-1 levels in patients with coronary artery disease and diabetes mellitus. Korean Circ J (2012) 42(2):100–6. 10.4070/kcj.2012.42.2.100 ] [
21. Topol EJ, McCarthy J, Gabriel S, Moliterno DJ, Rogers WJ, Newby LK, et al. . Single nucleotide polymorphisms in multiple novel thrombospondin genes may be associated with familial premature myocardial infarction. Circulation (2001) 104(22):2641–4. 10.1161/hc4701.100910 [] [[PubMed]
22. Frangogiannis NG, Ren G, Dewald O, Zymek P, Haudek S, Koerting A, et al. . Critical role of endogenous thrombospondin-1 in preventing expansion of healing myocardial infarcts. Circulation (2005) 111(22):2935–42. 10.1161/CIRCULATIONAHA.104.510354 [] [[PubMed]
23. DeLeon-Pennell KY, Mouton AJ, Ero OK, Ma Y, Padmanabhan Iyer R, Flynn ER, et al. . LXR/RXR signaling and neutrophil phenotype following myocardial infarction classify sex differences in remodeling. Basic Res Cardiol (2018) 113(5):40. 10.1007/s00395-018-0699-5 ] [
24. Ibrahimi A, Bonen A, Blinn WD, Hajri T, Li X, Zhong K, et al. . Muscle-specific overexpression of FAT/CD36 enhances fatty acid oxidation by contracting muscle, reduces plasma triglycerides and fatty acids, and increases plasma glucose and insulin. J Biol Chem (1999) 274(38):26761–6. 10.1074/jbc.274.38.26761 [] [[PubMed]
25. Febbraio M, Abumrad NA, Hajjar DP, Sharma K, Cheng W, Pearce SF, et al. . A null mutation in murine CD36 reveals an important role in fatty acid and lipoprotein metabolism. J Biol Chem (1999) 274(27):19055–62. 10.1074/jbc.274.27.19055 [] [[PubMed]
26. Febbraio M, Podrez EA, Smith JD, Hajjar DP, Hazen SL, Hoff HF, et al. . Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice. J Clin Invest (2000) 105(8):1049–56. 10.1172/JCI9259 ] [
27. Samovski D, Sun J, Pietka T, Gross RW, Eckel RH, Su X, et al. . Regulation of AMPK activation by CD36 links fatty acid uptake to β-oxidation. Diabetes (2015) 64(2):353–9. 10.2337/db14-0582 ] [
28. Gonzalez-Quesada C, Cavalera M, Biernacka A, Kong P, Lee DW, Saxena A, et al. . Thrombospondin-1 induction in the diabetic myocardium stabilizes the cardiac matrix in addition to promoting vascular rarefaction through angiopoietin-2 upregulation. Circ Res (2013) 113(12):1331–44. 10.1161/CIRCRESAHA.113.302593 ] [
29. Murphy-Ullrich JE. Thrombospondin 1 and Its Diverse Roles as a Regulator of Extracellular Matrix in Fibrotic Disease. J Histochem Cytochem (2019) 67(9):683–99. 10.1369/0022155419851103 ] [
30. Walton KL, Johnson KE, Harrison CA. Targeting TGF-β Mediated SMAD Signaling for the Prevention of Fibrosis. Front Pharmacol (2017) 8:461. 10.3389/fphar.2017.00461 ] [
31. Jana S, Zhang H, Lopaschuk GD, Freed DH, Sergi C, Kantor PF, et al. . Disparate Remodeling of the Extracellular Matrix and Proteoglycans in Failing Pediatric Versus Adult Hearts. J Am Heart Assoc (2018) 7(19):e010427. 10.1161/JAHA.118.010427 ] [
32. Kelm NQ, Beare JE, Weber GJ, LeBlanc AJ. Thrombospondin-1 mediates Drp-1 signaling following ischemia reperfusion in the aging heart. FASEB Bioadv (2020) 2(5):304–14. 10.1096/fba.2019-00090 ] [
33. Soto-Pantoja DR, Kaur S, Roberts DD. CD47 signaling pathways controlling cellular differentiation and responses to stress. Crit Rev Biochem Mol Biol (2015) 50(3):212–30. 10.3109/10409238.2015.1014024 ] [
34. Isenberg JS, Qin Y, Maxhimer JB, Sipes JM, Despres D, Schnermann J, et al. . Thrombospondin-1 and CD47 regulate blood pressure and cardiac responses to vasoactive stress. Matrix Biol (2009) 28(2):110–9. 10.1016/j.matbio.2009.01.002 ] [
35. Moura R, Tjwa M, Vandervoort P, Cludts K, Hoylaerts MF. Thrombospondin-1 activates medial smooth muscle cells and triggers neointima formation upon mouse carotid artery ligation. Arterioscler Thromb Vasc Biol (2007) 27(10):2163–9. 10.1161/ATVBAHA.107.151282 [] [[PubMed]
36. Raman P, Krukovets I, Marinic TE, Bornstein P, Stenina OI. Glycosylation mediates up-regulation of a potent antiangiogenic and proatherogenic protein, thrombospondin-1, by glucose in vascular smooth muscle cells. J Biol Chem (2007) 282(8):5704–14. 10.1074/jbc.M610965200 [] [[PubMed]
37. Kumar R, Mickael C, Kassa B, Gebreab L, Robinson JC, Koyanagi DE, et al. . TGF-β activation by bone marrow-derived thrombospondin-1 causes Schistosoma- and hypoxia-induced pulmonary hypertension. Nat Commun (2017) 8:15494. 10.1038/ncomms15494 ] [
38. Billaud M, Hill JC, Richards TD, Gleason TG, Phillippi JA. Medial Hypoxia and Adventitial Vasa Vasorum Remodeling in Human Ascending Aortic Aneurysm. Front Cardiovasc Med (2018) 5:124. 10.3389/fcvm.2018.00124 ] [
39. Labrousse-Arias D, Castillo-González R, Rogers NM, Torres-Capelli M, Barreira B, Aragonés J, et al. . HIF-2α-mediated induction of pulmonary thrombospondin-1 contributes to hypoxia-driven vascular remodelling and vasoconstriction. Cardiovasc Res (2016) 109(1):115–30. 10.1093/cvr/cvv243 ] [
40. Roberts DD, Miller TW, Rogers NM, Yao M, Isenberg JS. The matricellular protein thrombospondin-1 globally regulates cardiovascular function and responses to stress via CD47. Matrix Biol (2012) 31(3):162–9. 10.1016/j.matbio.2012.01.005 ] [
41. Yao M, Roberts DD, Isenberg JS. Thrombospondin-1 inhibition of vascular smooth muscle cell responses occurs via modulation of both cAMP and cGMP. Pharmacol Res (2011) 63(1):13–22. 10.1016/j.phrs.2010.10.014 ] [
42. Stenina-Adognravi O. Invoking the Power of Thrombospondins: Regulation of Thrombospondins Expression. Matrix Biol (2014) 0:69–82. 10.1016/j.matbio.2014.02.001 ] [
43. Nevitt C, McKenzie G, Christian K, Austin J, Hencke S, Hoying J, et al. . Physiological levels of thrombospondin-1 decrease NO-dependent vasodilation in coronary microvessels from aged rats. Am J Physiol Heart Circ Physiol (2016) 310(11):H1842–1850. 10.1152/ajpheart.00086.2016 ] [
44. Rogers NM, Sharifi-Sanjani M, Csányi G, Pagano PJ, Isenberg JS. Thrombospondin-1 and CD47 regulation of cardiac, pulmonary and vascular responses in health and disease. Matrix Biol (2014) 37:92–101. 10.1016/j.matbio.2014.01.002 ] [
45. Ghimire K, Li Y, Chiba T, Julovi SM, Li J, Ross MA, et al. . CD47 Promotes Age-Associated Deterioration in Angiogenesis, BloodFlow and Glucose Homeostasis. Cells (2020) 9(7):1695. 10.3390/cells9071695 ] [
46. Moura R, Tjwa M, Vandervoort P, Van Kerckhoven S, Holvoet P, Hoylaerts MF. Thrombospondin-1 deficiency accelerates atherosclerotic plaque maturation in ApoE-/- mice. Circ Res (2008) 103(10):1181–9. 10.1161/CIRCRESAHA.108.185645 [] [[PubMed]
47. Kojima Y, Volkmer JP, McKenna K, Civelek M, Lusis AJ, Miller CL, et al. . CD47-blocking antibodies restore phagocytosis and prevent atherosclerosis. Nature (2016) 536(7614):86–90. 10.1038/nature18935 ] [
48. Morrissey MA, Kern N, Vale RD. CD47 Ligation Repositions the Inhibitory Receptor SIRPA to Suppress Integrin Activation and Phagocytosis. Immunity (2020) 53(2):290–302.e296. 10.1016/j.immuni.2020.07.008 ] [
49. Nath PR, Pal-Nath D, Mandal A, Cam MC, Schwartz AL, Roberts DD. Natural Killer Cell Recruitment and Activation Are Regulated by CD47 Expression in the Tumor Microenvironment. Cancer Immunol Res (2019) 7(9):1547–61. 10.1158/2326-6066.CIR-18-0367 ] [
50. Maile LA, Clemmons DR. Integrin-associated protein binding domain of thrombospondin-1 enhances insulin-like growth factor-I receptor signaling in vascular smooth muscle cells. Circ Res (2003) 93(10):925–31. 10.1161/01.RES.0000101754.33652.B7 [] [[PubMed]
51. Wang Y, Nanda V, Direnzo D, Ye J, Xiao S, Kojima Y, et al. . Clonally expanding smooth muscle cells promote atherosclerosis by escaping efferocytosis and activating the complement cascade. Proc Natl Acad Sci USA (2020) 117(27):15818–26. 10.1073/pnas.2006348117 ] [
52. Maimaitiyiming H, Clemons K, Zhou Q, Norman H, Wang S. Thrombospondin1 deficiency attenuates obesity-associated microvascular complications in ApoE-/- mice. PLoS One (2015) 10(3):e0121403. 10.1371/journal.pone.0121403 ] [
53. Stenina OI, Plow EF. Counterbalancing forces: what is thrombospondin-1 doing in atherosclerotic lesions? Circ Res (2008) 103(10):1053–5. 10.1161/CIRCRESAHA.108.188870 ] [
54. Li Z, Calzada MJ, Sipes JM, Cashel JA, Krutzsch HC, Annis DS, et al. . Interactions of thrombospondins with alpha4beta1 integrin and CD47 differentially modulate T cell behavior. J Cell Biol (2002) 157(3):509–19. 10.1083/jcb.200109098 ] [
55. Kim CW, Pokutta-Paskaleva A, Kumar S, Timmins LH, Morris AD, Kang DW, et al. . Disturbed Flow Promotes Arterial Stiffening Through Thrombospondin-1. Circulation (2017) 136(13):1217–32. 10.1161/CIRCULATIONAHA.116.026361 ] [
56. Zeng T, Yuan J, Gan J, Liu Y, Shi L, Lu Z, et al. . Thrombospondin 1 Is Increased in the Aorta and Plasma of Patients With Acute Aortic Dissection. Can J Cardiol (2019) 35(1):42–50. 10.1016/j.cjca.2018.11.008 [] [[PubMed]
57. Emonard H, Duca L, Dedieu S. Editorial: Matricellular Receptors As Potential Targets in Anti-Cancer Therapeutic Strategies. Front Pharmacol (2016) 7:95. 10.3389/fphar.2016.00095 ] [
58. Isenberg JS, Romeo MJ, Yu C, Yu CK, Nghiem K, Monsale J, et al. . Thrombospondin-1 stimulates platelet aggregation by blocking the antithrombotic activity of nitric oxide/cGMP signaling. Blood (2008) 111(2):613–23. 10.1182/blood-2007-06-098392 ] [
59. Aburima A, Berger M, Spurgeon BE, Webb BA, Wraith KS, Febbraio M, et al. . Thrombospondin-1 promotes haemostasis through modulation of cAMPsignalling in blood platelets. Blood (2021) 137(5):678–89. 10.1182/blood.2020005382 [] [[PubMed]
60. Kuijpers MJ, de Witt S, Nergiz-Unal R, van Kruchten R, Korporaal SJ, Verhamme P, et al. . Supporting roles of platelet thrombospondin-1 and CD36 in thrombus formation on collagen. Arterioscler Thromb Vasc Biol (2014) 34(6):1187–92. 10.1161/ATVBAHA.113.302917 [] [[PubMed]
61. Jeanne A, Sarazin T, Charlé M, Kawecki C, Kauskot A, Hedtke T, et al. . Towards the Therapeutic Use of Thrombospondin 1/CD47 Targeting TAX2 Peptide as an Antithrombotic Agent. Arterioscler Thromb Vasc Biol (2021) 41(1):e1–e17. 10.1161/ATVBAHA.120.314571 [] [[PubMed]
62. Drott CJ, Olerud J, Emanuelsson H, Christoffersson G, Carlsson PO. Sustained beta-cell dysfunction but normalized islet mass in aged thrombospondin-1 deficient mice. PLoS One (2012) 7(10):e47451. 10.1371/journal.pone.0047451 ] [
63. Olerud J, Mokhtari D, Johansson M, Christoffersson G, Lawler J, Welsh N, et al. . Thrombospondin-1: an islet endothelial cell signal of importance for β-cell function. Diabetes (2011) 60(7):1946–54. 10.2337/db10-0277 ] [
64. de Souza BM, Michels M, Sortica DA, Bouças AP, Rheinheimer J, Buffon MP, et al. . Polymorphisms of the UCP2 Gene Are Associated with Glomerular Filtration Rate in Type 2 Diabetic Patients and with Decreased UCP2 Gene Expression in Human Kidney. PLoS One (2015) 10(7):e0132938. 10.1371/journal.pone.0132938 ] [
65. Brissova M, Shostak A, Shiota M, Wiebe PO, Poffenberger G, Kantz J, et al. . Pancreatic islet production of vascular endothelial growth factor–a is essential for islet vascularization, revascularization, and function. Diabetes (2006) 55(11):2974–85. 10.2337/db06-0690 [] [[PubMed]
66. Wang S, Wu X, Lincoln TM, Murphy-Ullrich JE. Expression of constitutively active cGMP-dependent protein kinase prevents glucose stimulation of thrombospondin 1 expression and TGF-beta activity. Diabetes (2003) 52(8):2144–50. 10.2337/diabetes.52.8.2144 [] [[PubMed]
67. Wang S, Skorczewski J, Feng X, Mei L, Murphy-Ullrich JE. Glucose up-regulates thrombospondin 1 gene transcription and transforming growth factor-beta activity through antagonism of cGMP-dependent protein kinase repression via upstream stimulatory factor 2. J Biol Chem (2004) 279(33):34311–22. 10.1074/jbc.M401629200 [] [[PubMed]
68. Chi TF, Khoder-Agha F, Mennerich D, Kellokumpu S, Miinalainen I, Kietzmann T, et al. . Loss of USF2 promotes proliferation, migration and mitophagy in a redox-dependent manner. Redox Biol (2020) 37:101750. 10.1016/j.redox.2020.101750 ] [
69. Lopez-Dee ZP, Chittur SV, Patel H, Chinikaylo A, Lippert B, Patel B, et al. . Thrombospondin-1 in a Murine Model of Colorectal Carcinogenesis. PLoS One (2015) 10(10):e0139918. 10.1371/journal.pone.0139918 ] [
70. Gutierrez LS, Suckow M, Lawler J, Ploplis VA, Castellino FJ. Thrombospondin 1–a regulator of adenoma growth and carcinoma progression in the APC(Min/+) mouse model. Carcinogenesis (2003) 24(2):199–207. 10.1093/carcin/24.2.199 [] [[PubMed]
71. Lan CC, Wu CS, Huang SM, Wu IH, Chen GS. High-glucose environment enhanced oxidative stress and increased interleukin-8 secretion from keratinocytes: new insights into impaired diabetic wound healing. Diabetes (2013) 62(7):2530–8. 10.2337/db12-1714 ] [
72. Mohanty P, Hamouda W, Garg R, Aljada A, Ghanim H, Dandona P. Glucose challenge stimulates reactive oxygen species (ROS) generation by leucocytes. J Clin Endocrinol Metab (2000) 85(8):2970–3. 10.1210/jcem.85.8.6854 [] [[PubMed]
73. Wasserman DH, Wang TJ, Brown NJ. The Vasculature in Prediabetes. Circ Res (2018) 122(8):1135–50. 10.1161/CIRCRESAHA.118.311912 ] [
74. Maile LA, Capps BE, Miller EC, Allen LB, Veluvolu U, Aday AW, et al. . Glucose regulation of integrin-associated protein cleavage controls the response of vascular smooth muscle cells to insulin-like growth factor-I. Mol Endocrinol (2008) 22(5):1226–37. 10.1210/me.2007-0552 ] [
75. Maile LA, Gollahon K, Wai C, Byfield G, Hartnett ME, Clemmons D. Disruption of the association of integrin-associated protein (IAP) with tyrosine phosphatase non-receptor type substrate-1 (SHPS)-1 inhibits pathophysiological changes in retinal endothelial function in a rat model of diabetes. Diabetologia (2012) 55(3):835–44. 10.1007/s00125-011-2416-x ] [
76. Bitar MS. Diabetes Impairs Angiogenesis and Induces Endothelial CellSenescence by Up-Regulating Thrombospondin-CD47-Dependent Signaling. Int J Mol Sci (2019) 20(3):673. 10.3390/ijms20030673 ] [
77. Andrejeva G, Capoccia BJ, Hiebsch RR, Donio MJ, Darwech IM, Puro RJ, et al. . Novel SIRPα Antibodies That Induce Single-Agent Phagocytosisof Tumor Cells while Preserving T Cells. J Immunol (2021) 206(4):712–21. 10.4049/jimmunol.2001019 ] [
78. Puro RJ, Bouchlaka MN, Hiebsch RR, Capoccia BJ, Donio MJ, Manning PT, et al. . Development of AO-176, a Next-Generation Humanized Anti-CD47 Antibody with Novel Anticancer Properties and Negligible Red Blood Cell Binding. Mol Cancer Ther (2020) 19(3):835–46. 10.1158/1535-7163.MCT-19-1079 [] [[PubMed]
79. Miquilena-Colina ME, Lima-Cabello E, Sánchez-Campos S, García-Mediavilla MV, Fernández-Bermejo M, Lozano-Rodríguez T, et al. . Hepatic fatty acid translocase CD36 upregulation is associated with insulin resistance, hyperinsulinaemia and increased steatosis in non-alcoholic steatohepatitis and chronic hepatitis C. Gut (2011) 60(10):1394–402. 10.1136/gut.2010.222844 [] [[PubMed]
80. Miyaoka K, Kuwasako T, Hirano K, Nozaki S, Yamashita S, Matsuzawa Y. CD36 deficiency associated with insulin resistance. Lancet (2001) 357(9257):686–7. 10.1016/s0140-6736(00)04138-6 [] [[PubMed]
81. Leder L, Kolehmainen M, Narverud I, Dahlman I, Myhrstad MC, de Mello VD, et al. . Effects of a healthy Nordic diet on gene expression changes in peripheral blood mononuclear cells in response to an oral glucose tolerance test in subjects with metabolic syndrome: a SYSDIET sub-study. Genes Nutr (2016) 11:3. 10.1186/s12263-016-0521-4 ] [
82. Samovski D, Dhule P, Pietka T, Jacome-Sosa M, Penrose E, Son NH, et al. . Regulation of Insulin Receptor Pathway and Glucose Metabolism by CD36 Signaling. Diabetes (2018) 67(7):1272–84. 10.2337/db17-1226 ] [
83. Isenberg JS, Jia Y, Fukuyama J, Switzer CH, Wink DA, Roberts DD. Thrombospondin-1 inhibits nitric oxide signaling via CD36 by inhibiting myristic acid uptake. J Biol Chem (2007) 282(21):15404–15. 10.1074/jbc.M701638200 ] [
84. Bai J, Xia M, Xue Y, Ma F, Cui A, Sun Y, et al. . Thrombospondin 1 improves hepatic steatosis in diet-induced insulin-resistant mice and is associated with hepatic fat content in humans. EBioMedicine (2020) 57:102849. 10.1016/j.ebiom.2020.102849 ] [
85. Son NH, Basu D, Samovski D, Pietka TA, Peche VS, Willecke F, et al. . Endothelial cell CD36 optimizes tissue fatty acid uptake. J Clin Invest (2018) 128(10):4329–42. 10.1172/JCI99315 ] [
86. Yang P, Zeng H, Tan W, Luo X, Zheng E, Zhao L, et al. . Loss of CD36 impairs hepatic insulin signaling by enhancing theinteraction of PTP1B with IR. FASEB J (2020) 34(4):4813–5992. 10.1096/fj.201902777RR [] [[PubMed]
87. Bhattacharyya S, Sul K, Krukovets I, Nestor C, Li J, Adognravi OS. Novel tissue-specific mechanism of regulation of angiogenesis and cancer growth in response to hyperglycemia. J Am Heart Assoc (2012) 1(6):e005967. 10.1161/JAHA.112.005967 ] [
88. Asama H, Suzuki R, Hikichi T, Takagi T, Masamune A, Ohira H. MicroRNA let-7d targets thrombospondin-1 and inhibits the activationof human pancreatic stellate cells. Pancreatology (2019) 19(1):196–203. 10.1016/j.pan.2018.10.012 [] [[PubMed]
89. Liu Y, Dong J, Ren B. MicroRNA-182-5p contributes to the protective effects of thrombospondin 1 against lipotoxicity in INS-1 cells. Exp Ther Med (2018) 16(6):5272–9. 10.3892/etm.2018.6883 ] [
90. Xia Y, Dobaczewski M, Gonzalez-Quesada C, Chen W, Biernacka A, Li N, et al. . Endogenous thrombospondin 1 protects the pressure-overloaded myocardium by modulating fibroblast phenotype and matrix metabolism. Hypertension (2011) 58(5):902–11. 10.1161/HYPERTENSIONAHA.111.175323 ] [
91. Aiken J, Mandel ER, Riddell MC, Birot O. Hyperglycaemia correlates with skeletal muscle capillary regression and is associated with alterations in the murine double minute-2/forkhead box O1/thrombospondin-1 pathway in type 1 diabetic BioBreeding rats. Diabetes Vasc Dis Res (2019) 16(1):28–37. 10.1177/1479164118805928 [] [[PubMed]
92. Klaassen I, de Vries EW, Vogels IMC, van Kampen AHC, Bosscha MI, Steel DHW, et al. . Identification of proteins associated with clinical and pathological features of proliferative diabetic retinopathy in vitreous and fibrovascular membranes. PLoS One (2017) 12(11):e0187304. 10.1371/journal.pone.0187304 ] [
93. Stenina OI, Krukovets I, Wang K, Zhou Z, Forudi F, Penn MS, et al. . Increased expression of thrombospondin-1 in vessel wall of diabetic Zucker rat. Circulation (2003) 107(25):3209–15. 10.1161/01.CIR.0000074223.56882.97 [] [[PubMed]
94. Varma V, Yao-Borengasser A, Bodles AM, Rasouli N, Phanavanh B, Nolen GT, et al. . Thrombospondin-1 is an adipokine associated with obesity, adipose inflammation, and insulin resistance. Diabetes (2008) 57(2):432–9. 10.2337/db07-0840 ] [
95. Matsugi K, Hosooka T, Nomura K, Ogawa W. Thrombospondin 1 Suppresses Insulin Signaling in C2C12 Myotubes. Kobe J Med Sci (2016) 62(1):E13–18.
96. Saboory E, Gholizadeh-Ghaleh Aziz S, Samadi M, Biabanghard A, Chodari L. Exercise and IGF-1 supplementation improve angiogenesis and angiogenic cytokines in a rat model of diabetes-induced neuropathy. Exp Physiol (2020) 105(5):783–92. 10.1113/EP088069 [] [[PubMed]
97. Wahab NA, Schaefer L, Weston BS, Yiannikouris O, Wright A, Babelova A, et al. . Glomerular expression of thrombospondin-1, transforming growth factor beta and connective tissue growth factor at different stages of diabetic nephropathy and their interdependent roles in mesangial response to diabetic stimuli. Diabetologia (2005) 48(12):2650–60. 10.1007/s00125-005-0006-5 [] [[PubMed]
98. Lu A, Miao M, Schoeb TR, Agarwal A, Murphy-Ullrich JE. Blockade of TSP1-dependent TGF-β activity reduces renal injury and proteinuria in a murine model of diabetic nephropathy. Am J Pathol (2011) 178(6):2573–86. 10.1016/j.ajpath.2011.02.039 ] [
99. Jiang N, Zhang Z, Shao X, Jing R, Wang C, Fang W, et al. . Blockade of thrombospondin-1 ameliorates high glucose-induced peritoneal fibrosis through downregulation of TGF-β1/Smad3 signaling pathway. J Cell Physiol (2020) 235(1):364–79. 10.1002/jcp.28976 [] [[PubMed]
100. von Toerne C, Huth C, de Las Heras Gala T, Kronenberg F, Herder C, Koenig W, et al. . MASP1, THBS1, GPLD1 and ApoA-IV are novel biomarkers associated with prediabetes: the KORA F4 study. Diabetologia (2016) 59(9):1882–92. 10.1007/s00125-016-4024-2 [] [[PubMed]
101. Matsuo Y, Tanaka M, Yamakage H, Sasaki Y, Muranaka K, Hata H, et al. . Thrombospondin 1 as a novel biological marker of obesity and metabolic syndrome. Metabolism (2015) 64(11):1490–9. 10.1016/j.metabol.2015.07.016 ] [
102. Dameron KM, Volpert OV, Tainsky MA, Bouck N. Control of angiogenesis in fibroblasts by p53 regulation of thrombospondin-1. Science (1994) 265(5178):1582–4. 10.1126/science.7521539 [] [[PubMed]
103. Kong P, Gonzalez-Quesada C, Li N, Cavalera M, Lee DW, Frangogiannis NG. Thrombospondin-1 regulates adiposity and metabolic dysfunction in diet-induced obesity enhancing adipose inflammation and stimulating adipocyte proliferation. Am J Physiol Endocrinol Metab (2013) 305(3):E439–450. 10.1152/ajpendo.00006.2013 ] [
104. Voros G, Lijnen HR. Deficiency of thrombospondin-1 in mice does not affect adipose tissue development. J Thromb Haemost (2006) 4(1):277–8. 10.1111/j.1538-7836.2005.01696.x [] [[PubMed]
105. Hida K, Wada J, Zhang H, Hiragushi K, Tsuchiyama Y, Shikata K, et al. . Identification of genes specifically expressed in the accumulatedvisceral adipose tissue of OLETF rats. J Lipid Res (2000) 41(10):1615–22. 10.1016/S0022-2275(20)31994-5 [] [[PubMed]
106. Ramis JM, Franssen-van Hal NL, Kramer E, Llado I, Bouillaud F, Palou A, et al. . Carboxypeptidase E and thrombospondin-1 are differently expressed in subcutaneous and visceral fat of obese subjects. Cell Mol Life Sci (2002) 59(11):1960–71. 10.1007/pl00012518 [] [[PubMed]
107. Efimenko A, Starostina E, Kalinina N, Stolzing A. Angiogenic properties of aged adipose derived mesenchymal stem cells after hypoxic conditioning. J Transl Med (2011) 9:10. 10.1186/1479-5876-9-10 ] [
108. Rittig K, Dolderer JH, Balletshofer B, Machann J, Schick F, Meile T, et al. . The secretion pattern of perivascular fat cells is different from that of subcutaneous and visceral fat cells. Diabetologia (2012) 55(5):1514–25. 10.1007/s00125-012-2481-9 [] [[PubMed]
109. Corvera S, Gealekman O. Adipose tissue angiogenesis: impact on obesity and type-2 diabetes. Biochim Biophys Acta (2014) 1842(3):463–72. 10.1016/j.bbadis.2013.06.003 ] [
110. Shimizu I, Aprahamian T, Kikuchi R, Shimizu A, Papanicolaou KN, MacLauchlan S, et al. . Vascular rarefaction mediates whitening of brown fat in obesity. J Clin Invest (2014) 124(5):2099–112. 10.1172/JCI71643 ] [
111. Wang D, Zhang Z, O’Loughlin E, Lee T, Houel S, O’Carroll D, et al. . Quantitative functions of Argonaute proteins in mammalian development. Genes Dev (2012) 26(7):693–704. 10.1101/gad.182758.111 ] [
112. Tang X, Miao Y, Luo Y, Sriram K, Qi Z, Lin FM, et al. . Suppression of Endothelial AGO1 Promotes Adipose Tissue Browning and Improves Metabolic Dysfunction. Circulation (2020) 142(4):365–79. 10.1161/CIRCULATIONAHA.119.041231 ] [
113. Memetimin H, Li D, Tan K, Zhou C, Liang Y, Wu Y, et al. . Myeloid-specific deletion of thrombospondin 1 protects against inflammation and insulin resistance in long-term diet-induced obese male mice. Am J Physiol Endocrinol Metab (2018) 315(6):E1194–203. 10.1152/ajpendo.00273.2018 ] [
114. Bréchot N, Gomez E, Bignon M, Khallou-Laschet J, Dussiot M, Cazes A, et al. . Modulation of macrophage activation state protects tissue from necrosis during critical limb ischemia in thrombospondin-1-deficient mice. PLoS One (2008) 3(12):e3950. 10.1371/journal.pone.0003950 ] [
115. Li Y, Tong X, Rumala C, Clemons K, Wang S. Thrombospondin1 deficiency reduces obesity-associated inflammation and improves insulin sensitivity in a diet-induced obese mouse model. PLoS One (2011) 6(10):e26656. 10.1371/journal.pone.0026656 ] [
116. Lopez-Dee ZP, Chittur SV, Patel B, Stanton R, Wakeley M, Lippert B, et al. . Thrombospondin-1 type 1 repeats in a model of inflammatory bowel disease: transcript profile and therapeutic effects. PLoS One (2012) 7(4):e34590. 10.1371/journal.pone.0034590 ] [
117. Matuszewska K, Santry LA, van Vloten JP, AuYeung AWK, Major PP, Lawler J, et al. . Combining Vascular Normalization with an Oncolytic Virus Enhances Immunotherapy in a Preclinical Model of Advanced-Stage Ovarian Cancer. Clin Cancer Res (2019) 25(5):1624–38. 10.1158/1078-0432.CCR-18-0220 [] [[PubMed]
118. Kennedy DJ, Kuchibhotla S, Westfall KM, Silverstein RL, Morton RE, Febbraio M. A CD36-dependent pathway enhances macrophage and adipose tissue inflammation and impairs insulin signalling. Cardiovasc Res (2011) 89(3):604–13. 10.1093/cvr/cvq360 ] [
119. Cui W, Maimaitiyiming H, Zhou Q, Norman H, Zhou C, Wang S. Interaction of thrombospondin1 and CD36 contributes to obesity-associated podocytopathy. Biochim Biophys Acta (2015) 1852(7):1323–33. 10.1016/j.bbadis.2015.03.010 ] [
120. Su T, Huang C, Yang C, Jiang T, Su J, Chen M, et al. . Apigenin inhibits STAT3/CD36 signaling axis and reduces visceral obesity. Pharmacol Res (2020) 152:104586. 10.1016/j.phrs.2019.104586 [] [[PubMed]
121. Gutierrez LS, Ling J, Nye D, Papathomas K, Dickinson C. Thrombospondin peptide ABT-898 inhibits inflammation and angiogenesis in a colitis model. World J Gastroenterol (2015) 21(20):6157–66. 10.3748/wjg.v21.i20.6157 ] [
122. Norman-Burgdolf H, Li D, Sullivan P, Wang S. CD47 differentially regulates white and brown fatfunction. Biol Open (2020) 9(12):bio056747. 10.1242/bio.056747 ] [
123. Reverte-Salisa L, Sanyal A, Pfeifer A. Role of cAMP and cGMP Signaling in Brown Fat. Handb Exp Pharmacol (2019) 251:161–82. 10.1007/164_2018_117 [] [[PubMed]
124. Mitschke MM, Hoffmann LS, Gnad T, Scholz D, Kruithoff K, Mayer P, et al. . Increased cGMP promotes healthy expansion and browning of white adipose tissue. FASEB J (2013) 27(4):1621–30. 10.1096/fj.12-221580 [] [[PubMed]
125. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab (2004) 89(6):2548–56. 10.1210/jc.2004-0395 [] [[PubMed]
126. Farr OM, Gavrieli A, Mantzoros CS. Leptin applications in 2015: what have we learned about leptin and obesity? Curr Opin Endocrinol Diabetes Obes (2015) 22(5):353–9. 10.1097/MED.0000000000000184 ] [
127. Ganguly R, Khanal S, Mathias A, Gupta S, Lallo J, Sahu S, et al. . TSP-1 (Thrombospondin-1) Deficiency Protects ApoE. Arterioscler Thromb Vasc Biol (2021) 41:e112–27. 10.1161/ATVBAHA.120.314962 [] [[PubMed]
128. Chavez RJ, Haney RM, Cuadra RH, Ganguly R, Adapala RK, Thodeti CK, et al. . Upregulation of thrombospondin-1 expression by leptin in vascular smooth muscle cells via JAK2- and MAPK-dependent pathways. Am J Physiol Cell Physiol (2012) 303(2):C179–191. 10.1152/ajpcell.00008.2012 [] [[PubMed]
129. Elaïb Z, Lopez JJ, Coupaye M, Zuber K, Becker Y, Kondratieff A, et al. . Platelet Functions are Decreased in Obesity and Restored after Weight Loss: Evidence for a Role of the SERCA3-Dependent ADP Secretion Pathway. Thromb Haemost (2019) 119(3):384–96. 10.1055/s-0038-1677033 [] [[PubMed]
130. Abu-Farha M, Tiss A, Abubaker J, Khadir A, Al-Ghimlas F, Al-Khairi I, et al. . Proteomics analysis of human obesity reveals the epigenetic factor HDAC4 as a potential target for obesity. PLoS One (2013) 8(9):e75342. 10.1371/journal.pone.0075342 ] [