{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:21:11Z","timestamp":1790364071725,"version":"4.1.0"},"reference-count":318,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2017,10,1]],"date-time":"2017-10-01T00:00:00Z","timestamp":1506816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,10,1]],"date-time":"2017-10-01T00:00:00Z","timestamp":1506816000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants & Redox Signaling"],"published-print":{"date-parts":[[2017,10]]},"abstract":"\n Significance:<\/jats:title>\n \n In contrast to structural elements of the extracellular matrix, matricellular proteins appear transiently during development and injury responses, but their sustained expression can contribute to chronic disease. Through interactions with other matrix components and specific cell surface receptors, matricellular proteins regulate multiple signaling pathways, including those mediated by reactive oxygen and nitrogen species and H\n 2<\/jats:sub>\n S. Dysregulation of matricellular proteins contributes to the pathogenesis of vascular diseases and cancer. Defining the molecular mechanisms and receptors involved is revealing new therapeutic opportunities.\n <\/jats:p>\n <\/jats:sec>\n \n Recent Advances:<\/jats:title>\n \n Thrombospondin-1 (TSP1) regulates NO, H\n 2<\/jats:sub>\n S, and superoxide production and signaling in several cell types. The TSP1 receptor CD47 plays a central role in inhibition of NO signaling, but other TSP1 receptors also modulate redox signaling. The matricellular protein CCN1 engages some of the same receptors to regulate redox signaling, and ADAMTS1 regulates NO signaling in Marfan syndrome. In addition to mediating matricellular protein signaling, redox signaling is emerging as an important pathway that controls the expression of several matricellular proteins.\n <\/jats:p>\n <\/jats:sec>\n \n Critical Issues:<\/jats:title>\n Redox signaling remains unexplored for many matricellular proteins. Their interactions with multiple cellular receptors remains an obstacle to defining signaling mechanisms, but improved transgenic models could overcome this barrier.<\/jats:p>\n <\/jats:sec>\n \n Future Directions:<\/jats:title>\n \n Therapeutics targeting the TSP1 receptor CD47 may have beneficial effects for treating cardiovascular disease and cancer and have recently entered clinical trials. Biomarkers are needed to assess their effects on redox signaling in patients and to evaluate how these contribute to their therapeutic efficacy and potential side effects.\n Antioxid. Redox Signal.<\/jats:italic>\n 27, 874\u2013911.\n <\/jats:p>\n <\/jats:sec>\n \n Table of Contents<\/jats:title>\n \n \n \n \n I.\u2002Introduction<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n A.\u2002What are matricellular proteins?<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n B.\u2002Historical evidence linking matricellular proteins and redox signaling<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n II.\u2002Thrombospondin-1 and NO Signaling<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n A.\u2002Thrombospondin-1 structure and receptors<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n B.\u2002Thrombospondin-1 regulation of NO synthesis<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n C.\u2002Thrombospondin-1 regulation of soluble guanylate cyclase and downstream targets<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\u2003\u2003\n 1.\u2002Soluble guanylate cyclase<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\u2003\u2003\n 2.\u2002cGMP-dependent protein kinase<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n D.\u2002Physiological functions of TSP1\/CD47 regulation of NO signaling<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\u2003\u2003\n 1.\u2002Platelet homeostasis<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\u2003\u2003\n 2.\u2002Vascular perfusion<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\u2003\u2003\n 3.\u2002Central blood pressure<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n E.\u2002NO regulation of TSP1 expression<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n III.\u2002NO Signaling and Other Matricellular Proteins<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n A.\u2002NO signaling and other thrombospondins<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\u2003\u2003\n 1.\u2002Regulation of NO signaling<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\u2003\u2003\n 2.\u2002Regulation of expression by NO<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n B.\u2002Regulation of iNOS-derived NO production and signaling<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\u2003\u2003\n 1.\u2002ADAMTS1<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\u2003\u2003\n 2.\u2002Osteopontin and NOS2 signaling<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\u2003\u2003\n 3.\u2002Regulation of other matricellular protein expression by NO<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \n IV.\u2002Thrombospondin-1 Regulation of H\n 2<\/jats:sub>\n S Biosynthesis and Signaling\n <\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n \n A.\u2002Role of H\n 2<\/jats:sub>\n S in T cell activation\n <\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n \n B.\u2002TSP1 inhibition of H\n 2<\/jats:sub>\n S biosynthesis in T cells\n <\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n \n C.\u2002Potential role of TSP1 in other H\n 2<\/jats:sub>\n S signaling\n <\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \n V.\u2002H\n 2<\/jats:sub>\n S Regulation of Matricellular Protein Expression\n <\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n A.\u2002Osteopontin<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n B.\u2002Tenascin C<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n C.\u2002Laminin-\u03b31<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n VI.\u2002TSP1 Regulation of ROS<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n A.\u2002TSP1 and ROS signaling in inflammatory cells<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\u2003\u2003\n 1.\u2002Historical context<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\u2003\u2003\n 2.\u2002Roles of TSP1 receptors<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\u2003\u2003\n 3.\u2002Role of the CD47 counter-receptor SIRP\u03b1<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n B.\u2002TSP1 and ROS signaling in vascular and renal cells<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n C.\u2002TSP1 and ROS signaling in vivo<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n VII.\u2002ROS Regulation by Other Matricellular Proteins<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n A.\u2002CCN1<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n B.\u2002Periostin<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n C.\u2002Tenascin-C<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n D.\u2002Caveats<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n VIII.\u2002CD47 Regulation of Redox Homeostasis in Irradiated Cells<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n A.\u2002NO and radiosensitivity<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n B.\u2002CD47-dependent regulation of redox metabolites in irradiated cells<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n C.\u2002CD47 regulation of mitochondrial redox<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n IX.\u2002TSP1\/CD47 Regulation of Stem Cell and Tissue Self-Renewal<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n A.\u2002Redox signaling in stem cells<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n B.\u2002TSP1 and CD47 in stem cell self-renewal and tissue regeneration<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n X.\u2002Therapeutic Opportunities to Improve Redox Signaling<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n A.\u2002Dysregulation of NO signaling by TSP1\/CD47 in clinical disease<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\u2003\u2003\n 1.\u2002Association of elevated TSP1 with impaired NO signaling in cardiovascular disease<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\u2003\u2003\n 2.\u2002Genetic dysregulation of TSP1 in cardiovascular disease<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\u2003\u2003\n 3.\u2002Circulating TSP1 as a biomarker of redox dysregulation<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\u2003\u2003\n 4.\u2002TSP1 in pulmonary disease<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\u2003\u2003\n 5.\u2002TSP1 and heart disease<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\u2003\u2003\n 6.\u2002TSP1 in aging<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\n B.\u2002Therapeutic targeting of the TSP1 receptor CD47<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\u2003\u2003\n 1.\u2002Applications for cardiovascular disease<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n \u2003\u2003\u2003\u2003\n 2.\u2002Therapeutic applications for cancer<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n \n \n XI.\u2002Conclusions and Outlook<\/jats:xref>\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1089\/ars.2017.7140","type":"journal-article","created":{"date-parts":[[2017,7,17]],"date-time":"2017-07-17T00:31:23Z","timestamp":1500251483000},"page":"874-911","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":28,"title":["Regulation of Cellular Redox Signaling by Matricellular Proteins in Vascular Biology, Immunology, and Cancer"],"prefix":"10.1177","volume":"27","author":[{"given":"David D.","family":"Roberts","sequence":"first","affiliation":[{"name":"National 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