Murine Hyaluronidase 2 Deficiency Results in Extracellular Hyaluronan Accumulation and Severe Cardiopulmonary Dysfunction

Chowdhury, Biswajit; Hemming, Richard; Hombach‐Klonisch, Sabine; Flamion, Bruno; Triggs-Raine, Barbara

doi:10.1074/jbc.m112.393629

Cited by 62 publications

(83 citation statements)

References 34 publications

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“…The expression of extracellular matrix (ECM)-degrading proteases [ctsba, ctssb.1 (ctss2.1), mmp9] and hyaluronidase 2 (hyal2), which degrades hyaluronan (Chowdhury et al, 2013), was increased in Notch-diminished hearts (Fig. 5A).…”

Section: Decreased Notch Signalling Affects Endothelial Cardiovasculmentioning

confidence: 99%

Notch signalling restricts inflammation and serpine1 expression in the dynamic endocardium of the regenerating zebrafish heart

et al. 2017

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The zebrafish heart regenerates after ventricular damage through a process involving inflammation, fibrotic tissue deposition/removal and myocardial regeneration. Using 3D whole-mount imaging, we reveal a highly dynamic endocardium during cardiac regeneration, including changes in cell morphology, behaviour and gene expression. These events lay the foundation for an initial expansion of the endocardium that matures to form a coherent endocardial structure within the injury site. We studied two important endocardial molecules, Serpine1 and Notch, which are implicated in different aspects of endocardial regeneration. Notch signalling regulates developmental gene expression and features of endocardial maturation. Also, Notch manipulation interferes with attenuation of the inflammatory response and cardiomyocyte proliferation and dedifferentiation. serpine1 is strongly expressed very early in the wound endocardium, with decreasing expression at later time points. serpine1 expression persists in Notch-abrogated hearts, via what appears to be a conserved mechanism. Functional inhibition studies show that Serpine1 controls endocardial maturation and proliferation and cardiomyocyte proliferation. Thus, we describe a highly dynamic endocardium in the regenerating zebrafish heart, with two key endocardial players, Serpine1 and Notch signalling, regulating crucial regenerative processes.

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Section: Decreased Notch Signalling Affects Endothelial Cardiovasculmentioning

confidence: 99%

Notch signalling restricts inflammation and serpine1 expression in the dynamic endocardium of the regenerating zebrafish heart

et al. 2017

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“…Hyal2 deficient mice displayed a significant increase in plasma HA and increased HA in the interstitial extracellular matrix of atrial cardiomyocytes [39, 40], suggesting that HYAL2 is essential for the breakdown of extracellular HA. Hyal2 deficient mice showed severe cardiopulmonary dysfunction [40].…”

Section: Introductionmentioning

confidence: 99%

“…Hyal2 deficient mice showed severe cardiopulmonary dysfunction [40]. Platelet-derived hyaluronidase 2 cleaves HA into fragments that trigger monocyte-mediated production of pro-inflammatory cytokines [41].…”

Section: Introductionmentioning

confidence: 99%

Hyaluronan as a therapeutic target in human diseases

Liang

Jiang

Noble

2016

Advanced Drug Delivery Reviews

187

117

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Accumulation and turnover of extracellular matrix is a hallmark of tissue injury, repair and remodeling in human diseases. Hyaluronan is a major component of the extracellular matrix and plays an important role in regulating tissue injury and repair, and controlling disease outcomes. The function of hyaluronan depends on its size, location, and interactions with binding partners. While fragmented hyaluronan stimulates the expression of an array of genes by a variety of cell types regulating inflammatory responses and tissue repair, cell surface hyaluronan provides protection against tissue damage from the environment and promotes regeneration and repair. The interactions of hyaluronan and its binding proteins participate in the pathogenesis of many human diseases. Thus, targeting hyaluronan and its interactions with cells and proteins may provide new approaches to developing therapeutics for inflammatory and fibrosing diseases. This review focuses on the role of hyaluronan in biological and pathological processes, and as a potential therapeutic target in human diseases.

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“…It was the first GAG discovered in 1934 by Karl Meyer and John W. Palmer 37 and, therefore, most comprehensively described in the heart. [38][39][40][41][42][43][44][45][46][47][48][49][50] The expression of hyaluronan is upregulated in experimental models of myocardial infarction (MI), 50 myocarditis, 51 and cardiac hypertrophy. 43,49 In 1985, West et al 52 demonstrated that oligosaccharides derived from high-molecular-weight hyaluronan can have very distinct functions compared with the large hyaluronan variants.…”

Section: Hyaluronan and Heparinmentioning

confidence: 99%

Myocardial Extracellular Matrix

Rienks

Papageorgiou

Frangogiannis

et al. 2014

Circulation Research

314

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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Murine Hyaluronidase 2 Deficiency Results in Extracellular Hyaluronan Accumulation and Severe Cardiopulmonary Dysfunction

Cited by 62 publications

References 34 publications

Notch signalling restricts inflammation and serpine1 expression in the dynamic endocardium of the regenerating zebrafish heart

Notch signalling restricts inflammation and serpine1 expression in the dynamic endocardium of the regenerating zebrafish heart

Hyaluronan as a therapeutic target in human diseases

Myocardial Extracellular Matrix

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