Matricellular Proteins

Roberts, David D.; Lau, Lester F.

doi:10.1007/978-3-642-16555-9_11

Cited by 12 publications

(12 citation statements)

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“…TSP1/CD47 signaling plays important roles in tumor and wound angiogenesis, fixed ischemic injuries, and ischemia/reperfusion injuries, and readers are referred to recent reviews (Frazier et al, 2010; Isenberg et al, 2008a; Isenberg et al, 2009b; Roberts and Lau, 2011). Elevated plasma TSP1 levels correlate positively with cardiovascular disease (Smadja et al, 2011), suggesting that TSP1 is a biomarker for and potentiator of vascular dysfunction.…”

Section: Pathophysiological Functions and Therapeutic Applicationsmentioning

confidence: 99%

“…Thrombospondin-1 (TSP1) is a matricellular protein that is transiently expressed in extracellular matrix and modulates cell function in a context-specific manner by engaging cell surface receptors and other components of the extracellular matrix (Bornstein, 1995; Roberts and Lau, 2011). TSP1 circulates at ~100 pM levels in plasma, and platelet α-granules represent a major preformed storage pool that can rapidly increase extracellular concentrations of the protein at sites of injury.…”

Section: Introductionmentioning

confidence: 99%

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The matricellular protein thrombospondin-1 globally regulates cardiovascular function and responses to stress via CD47

et al. 2012

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Matricellular proteins play diverse roles in modulating cell behavior by engaging specific cell surface receptors and interacting with extracellular matrix proteins, secreted enzymes, and growth factors. Studies of such interactions involving thrombospondin-1 have revealed several physiological functions and roles in the pathogenesis of injury responses and cancer, but the relatively mild phenotypes of mice lacking thrombospondin-1 suggested that thrombospondin-1 would not be a central player that could be exploited therapeutically. Recent research focusing on signaling through its receptor CD47, however, has uncovered more critical roles for thrombospondin-1 in acute regulation of cardiovascular dynamics, hemostasis, immunity, and mitochondrial homeostasis. Several of these functions are mediated by potent and redundant inhibition of the canonical nitric oxide pathway. Conversely, elevated tissue thrombospondin-1 levels in major chronic diseases of aging may account for the deficient nitric oxide signaling that characterizes these diseases, and experimental therapeutics targeting CD47 show promise for treating such chronic diseases as well as acute stress conditions that are associated with elevated thrombospondin-1 expression.

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Section: Pathophysiological Functions and Therapeutic Applicationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The matricellular protein thrombospondin-1 globally regulates cardiovascular function and responses to stress via CD47

et al. 2012

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“…Matricellular proteins are not constitutive structural elements of extracellular matrix, rather they function as regulatory molecules that are present in extracellular matrix at specific times during development, tissue remodeling, and responses to injury or chronic disease states. Thrombospondin-1 (TSP1) is a prototypical member of this family, which has grown to include four additional thrombospondins (TSPs), tenascins, periostin, the secreted protein acidic and rich in cysteine (SPARC) family, the five small integrin-binding ligand N-linked glycoprotein (SIB-LING) family members, the CCN (CYR61, CTGF [connective tissue growth factor], and NOV [nephroblastoma overexpressed gene]) family, and other thrombospondinrepeat (TSR)-containing proteins such as the a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family (142,169,209) (Fig. 1).…”

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confidence: 99%

Regulation of Cellular Redox Signaling by Matricellular Proteins in Vascular Biology, Immunology, and Cancer

Roberts

Kaur

Isenberg

2017

Antioxidants & Redox Signaling

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Significance: 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 2 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. Recent Advances: Thrombospondin-1 (TSP1) regulates NO, H 2 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. Critical Issues: 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. Future Directions: 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. Antioxid. Redox Signal. 27, 874-911.

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“…These proteins characteristically contain binding sites for some major structural elements in the matrix, binding sites for specific cell surface receptors, and in some cases domains that enzymatic alter other matrix components and that sequester or modulate the activities of specific growth factors. Such proteins have been classified as matricellular proteins [7,8]. The prototypical matricellular proteins were thrombospondin-1, tenascin-C, and secreted protein acidic and rich in cysteine (SPARC).…”

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confidence: 99%

“…The CCN family of cysteine-rich matricellular proteins contains 6 members in vertebrates [8,24]. These multidomain proteins are related to thrombospondins in that they contain a thrombospondin type 1 repeat.…”

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confidence: 99%