Hyaluronan cross-linking: a protective mechanism in inflammation?

Day, Anthony J.; Motte, Carol A. de la

doi:10.1016/j.it.2005.09.009

Cited by 291 publications

(328 citation statements)

References 45 publications

(106 reference statements)

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“…Several different mechanisms of crosslinking hyaluronan have been identified that can influence pericellular matrix assembly and material properties [32]. For example, the Cterminal lectin-like domain of versican has been shown to bind to multimeric tenascin-R and tenascin-C in a calcium-dependent manner, creating the possibility of crosslinking hyaluronan through non-covalent versican-tenascin-versican interactions [33,34].…”

Section: Hyaluronan Crosslinkingmentioning

confidence: 99%

“…TSG-6 (35 kDa-secreted product of the tumour necrosis factor-stimulated gene-6), is another protein with a Link module that serves in hyaluronan binding and participates with other proteins in the formation of higher-order crosslinked hyaluronan structures [32]. TSG-6 can act as a cofactor in the transfer of the IαI heavy chains to hyaluronan as described above.…”

Section: Hyaluronan Crosslinkingmentioning

confidence: 99%

“…These cables also contain versican, IαI heavy chains, and TSG-6 [47]. It has been proposed that the presentation of hyaluronan in a crosslinked form leads to receptor clustering on leukocytes (or co-receptor engagement through the presence of accessory molecules on the cables) which would promote adhesion [32,47]. It has been suggested that this may be proinflammatory, with the cables acting as distress signals that might perpetuate chronic inflammation [45].…”

Section: Hyaluronan Crosslinkingmentioning

confidence: 99%

“…It has been suggested that this may be proinflammatory, with the cables acting as distress signals that might perpetuate chronic inflammation [45]. Others have suggested that the cables could be anti-inflammatory and control leukocyte activation by preventing adhesion through ICAM-1 [48], VCAM-1 or VLA-4 [49], or by preventing loss of matrix [32,47].…”

Section: Hyaluronan Crosslinkingmentioning

confidence: 99%

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Hyaluronan-dependent pericellular matrix☆

Evanko¹,

Tammi²,

Tammi³

et al. 2007

Advanced Drug Delivery Reviews

255

238

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Hyaluronan is a multifunctional glycosaminoglycan that forms the structural basis of the pericellular matrix. Hyaluronan is extruded directly through the plasma membrane by one of three hyaluronan synthases and anchored to the cell surface by the synthase or cell surface receptors such as CD44 or RHAMM. Aggregating proteoglycans and other hyaluronan-binding proteins, contribute to the material and biological properties of the matrix and regulate cell and tissue function. The pericellular matrix plays multiple complex roles in cell adhesion/de-adhesion, and cell shape changes associated with proliferation and locomotion. Time-lapse studies show that pericellular matrix formation facilitates cell detachment and mitotic cell rounding. Hyaluronan crosslinking occurs through various proteins, such as tenascin, TSG-6, inter-alpha-trypsin inhibitor, pentraxin and TSP-1. This creates higher order levels of structured hyaluronan that may regulate inflammation and other biological processes. Microvillous or filopodial membrane protrusions are created by active hyaluronan synthesis, and form the scaffold of hyaluronan coats in certain cells. The importance of the pericellular matrix in cellular mechanotransduction and the response to mechanical strain are also discussed.

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Section: Hyaluronan Crosslinkingmentioning

confidence: 99%

Section: Hyaluronan Crosslinkingmentioning

confidence: 99%

Section: Hyaluronan Crosslinkingmentioning

confidence: 99%

Section: Hyaluronan Crosslinkingmentioning

confidence: 99%

See 2 more Smart Citations

Hyaluronan-dependent pericellular matrix☆

Evanko¹,

Tammi²,

Tammi³

et al. 2007

Advanced Drug Delivery Reviews

255

238

View full text Add to dashboard Cite

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“…The selective recognition of fibroblast growth factor-2 (FGF-2) by PTX3 inhibits FGF-2 angiogenic activity on endothelial cells (12) and blocks the autocrine and paracrine stimulation exerted by FGF-2 on smooth muscle cells (13). Previous studies on Ptx3 Ϫ/Ϫ mice suggested that PTX3 acts as a central "node" in cumulus matrix organization by establishing multivalent contacts to the HA-binding protein tumor necrosis factor-stimulated gene-6 protein (TSG-6) (9,14,15) and the serum protein inter-␣-inhibitor (16). PTX3 also plays a role in regulating the scavenger activity of macrophages and dendritic cells by direct binding to apoptotic cells (17)(18)(19)(20).…”

mentioning

confidence: 99%

Structural Characterization of PTX3 Disulfide Bond Network and Its Multimeric Status in Cumulus Matrix Organization

Inforzato

Rivieccio²,

Morreale

et al. 2008

Journal of Biological Chemistry

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123

129

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PTX3 is an acute phase glycoprotein that plays key roles in resistance to certain pathogens and in female fertility. PTX3 exerts its functions by interacting with a number of structurally unrelated molecules, a capacity that is likely to rely on its complex multimeric structure stabilized by interchain disulfide bonds. In this study, PAGE analyses performed under both native and denaturing conditions indicated that human recombinant PTX3 is mainly composed of covalently linked octamers. The network of disulfide bonds supporting this octameric assembly was resolved by mass spectrometry and Cys to Ser site-directed mutagenesis. Here we report that cysteine residues at positions 47, 49, and 103 in the N-terminal domain form three symmetric interchain disulfide bonds stabilizing four protein subunits in a tetrameric arrangement. Additional interchain disulfide bonds formed by the C-terminal domain cysteines Cys 317 and Cys 318 are responsible for linking the PTX3 tetramers into octamers. We also identified three intrachain disulfide bonds within the C-terminal domain that we used as structural constraints to build a new three-dimensional model for this domain. Previously it has been shown that PTX3 is a key component of the cumulus oophorus extracellular matrix, which forms around the oocyte prior to ovulation, because cumuli from PTX3 ؊/؊ mice show defective matrix organization. Recombinant PTX3 is able to restore the normal phenotype ex vivo in cumuli from PTX3 ؊/؊ mice. Here we demonstrate that PTX3 Cys to Ser mutants, mainly assembled into tetramers, exhibited wild type rescue activity, whereas a mutant, predominantly composed of dimers, had impaired functionality. These findings indicate that protein oligomerization is essential for PTX3 activity within the cumulus matrix and implicate PTX3 tetramers as the functional molecular units required for cumulus matrix organization and stabilization.

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