Small leucine-rich proteoglycans orchestrate receptor crosstalk during inflammation

Moreth, Kristin; Iozzo, Renato V.; Schaefer, Liliana

doi:10.4161/cc.20316

Cited by 140 publications

(147 citation statements)

References 70 publications

(129 reference statements)

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“…After original identification of these proteoglycans in the bone and cartilage, 121 their involvement has expanded to cancer biology, immunity, and embryonic development. [122][123][124] As a result of their diverse protein cores and GAG side chains, SLRPs interact with various cytokines, growth factors, cell surface receptors, as well as other matrix proteins. Indeed, they can bind different types of collagens, 125 TLRs, 123 epidermal growth factor receptors and insulin growth factor receptors, 126 low-density lipoprotein receptors, 127 and TGF-β.…”

Section: Small Leucine-rich Proteoglycansmentioning

confidence: 99%

“…Indeed, they can bind different types of collagens, 125 TLRs, 123 epidermal growth factor receptors and insulin growth factor receptors, 126 low-density lipoprotein receptors, 127 and TGF-β. 128 These interactions illustrate the involvement of SLRPs in a wide range of cellular functions and pathophysiologic responses, including collagen fibril assembly, 125 inflammation, 123 cell proliferation, 126 atherosclerosis, 127 and fibrosis, 128 hence emphasizing their potential role in cardiac matrix biology.…”

Section: Small Leucine-rich Proteoglycansmentioning

confidence: 99%

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Myocardial Extracellular Matrix

Rienks

Papageorgiou

Frangogiannis

et al. 2014

Circulation Research

313

170

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Abstract:The cardiac extracellular matrix (ECM) is a complex architectural network consisting of structural and nonstructural proteins, creating strength and plasticity. The nonstructural compartment of the ECM houses a variety of proteins, which are vital for ECM plasticity, and can be divided into 3 major groups: glycoproteins, proteoglycans, and glycosaminoglycans. The common denominator for these groups is glycosylation, which refers to the decoration of proteins or lipids with sugars. This review will discuss the fundamental role of the matrix in cardiac development, homeostasis, and remodeling, from a glycobiology point of view. Glycoproteins (eg, thrombospondins, secreted protein acidic and rich in cysteine, tenascins), proteoglycans (eg, versican, syndecans, biglycan), and glycosaminoglycans (eg, hyaluronan, heparan sulfate) are upregulated on cardiac injury and regulate key processes in the remodeling myocardium such as inflammation, fibrosis, and angiogenesis. Albeit some parallels can be made regarding the processes these proteins are involved in, their specific functions are extremely diverse. In fact, under varying conditions, individual proteins can even have opposing functions, making spatiotemporal contribution of these proteins in the rearrangement of multifaceted ECM very hard to grasp. Alterations of protein characteristics by the addition of sugars may explain the immense, yet tightly regulated, variability of the remodeling cardiac matrix. Understanding the role of glycosylation in altering the ultimate function of glycoproteins, proteoglycans, and glycosaminoglycans in the myocardium may lead to the development of new biochemical structures or compounds with great therapeutic potential for patients with heart disease. (Circ Res. 2014;114:872-888.)

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Section: Small Leucine-rich Proteoglycansmentioning

confidence: 99%

Section: Small Leucine-rich Proteoglycansmentioning

confidence: 99%

Myocardial Extracellular Matrix

Rienks

Papageorgiou

Frangogiannis

et al. 2014

Circulation Research

313

170

View full text Add to dashboard Cite

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“…bacteria or viruses) release pathogenassociated molecular patterns (PAMPs) 2 that are recognized by pattern recognition receptors (PRRs) of the immune system and thus trigger an inflammatory response (1). In contrast, sterile inflammation, an important characteristic of myocardial infarction, atherosclerosis, several autoimmune diseases, and cancer, is induced by the release of endogenous molecules called DAMPs following tissue stress or injury (2)(3)(4)(5). PAMPs and DAMPs are highly conserved motifs derived from the pathogens themselves (PAMPs) or from self-molecules that are normally hidden from the PRRs by compartmentalization (intracellular DAMPs) or sequestration in the ECM (extracellular DAMPs).…”

mentioning

confidence: 99%

“…The molecular makeup of DAMPs is quite heterogeneous, ranging from the small uric acid or ATP molecules to large proteins Ͼ100 kDa in size and even organelles (11,12). In turn, this high structural diversity allows DAMPs to achieve cross-talk between PRRs and a wide variety of "non-immune" receptors, finally impacting on the complexity of DAMP signaling (5,7). In this review, I provide a critical appraisal of the diverse modalities of DAMP generation and discuss the major receptors and signaling pathways operating in DAMP-mediated inflammation.…”

mentioning

confidence: 99%

Complexity of Danger: The Diverse Nature of Damage-associated Molecular Patterns

Schaefer

2014

Journal of Biological Chemistry

Self Cite

532

467

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In reply to internal or external danger stimuli, the body orchestrates an inflammatory response. The endogenous triggers of this process are the damage-associated molecular patterns (DAMPs). DAMPs represent a heterogeneous group of molecules that draw their origin either from inside the various compartments of the cell or from the extracellular space. Following interaction with pattern recognition receptors in crosstalk with various non-immune receptors, DAMPs determine the downstream signaling outcome of septic and aseptic inflammatory responses. In this review, the diverse nature, structural characteristics, and signaling pathways elicited by DAMPs will be critically evaluated.

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“…Short leucine-dominant proteoglycans, including decorin and biglycan, may coordinate TLRs crosstalk during the course of inflammation [90,91]. Septic inflammation induces initial responses that comprise the activation of the decorin gene; the level of decorin protein is elevated in mouse models as well as plasma of septic patients, and high levels of decorin enhance the expression of pro-inflammatory molecules [90].…”

Section: Gall Bladder Cancermentioning

confidence: 99%

Cancer and the microbiome: potential applications as new tumor biomarker

Khan

Gil-Bazo

Castiglia

et al. 2014

Expert Review of Anticancer Therapy

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Authors contributed equallyMicrobial communities that colonize in humans are collectively described as microbiome. According to conservative estimates, about 15% of all types of neoplasms are related to different infective agents. However, current knowledge is not sufficient to explain how the microbiome contributes to the growth and development of cancers. Large and thorough studies involving colonized, diverse and complex microbiome entities are required to identify microbiome as a potential cancer marker and to understand how the immune system is involved in response to pathogens. This article reviews the existing evidence supporting the enigmatic association of transformed microbiome with the development of cancer through the immunological modification. Ascertaining the connection between microbiome and immunological responses with risk of cancer may direct to explaining significant advances in the etiology of cancer, potentially disclosing a novel paradigm of research for the management and prevention of cancer.

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Small leucine-rich proteoglycans orchestrate receptor crosstalk during inflammation

Cited by 140 publications

References 70 publications

Myocardial Extracellular Matrix

Myocardial Extracellular Matrix

Complexity of Danger: The Diverse Nature of Damage-associated Molecular Patterns

Cancer and the microbiome: potential applications as new tumor biomarker

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