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Sini, Patrizia; Denti, Antonella; Tira, Maria Enrica; Balduini, Cesare

doi:10.1023/a:1018550307649

Cited by 42 publications

(10 citation statements)

References 14 publications

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“…Notably, the amount of DCN on beads that was required to produce inhibition of collagen binding by cells was very low (3 ϫ 10 Ϫ20 mol of DCN bound/bead) and approached an equimolar ratio (0.34) with the amount of collagen on beads (8.7 ϫ 10 Ϫ20 mol of collagen bound/bead). DCN and Collagen Binding-Previous studies on DCN-collagen interactions have largely focused on modulation of collagen fibrillogenesis (9,10,20,(32)(33)(34). The novelty of the current report is that DCN inhibits the collagen binding step of phagocytosis as demonstrated by a consistent and marked reduction in collagen bead binding.…”

Section: Discussionmentioning

confidence: 73%

Collagen Phagocytosis by Fibroblasts Is Regulated by Decorin

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Laschinger

Arora

et al. 2005

Journal of Biological Chemistry

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Decorin is a small, leucine-rich proteoglycan that binds to collagen and regulates fibrillogenesis. We hypothesized that decorin binding to collagen inhibits phagocytosis of collagen fibrils. To determine the effects of decorin on collagen degradation, we analyzed phagocytosis of collagen and collagen/decorin-coated fluorescent beads by Rat-2 and gingival fibroblasts. Collagen beads bound to gingival cells by ␣2␤1 integrins. Binding and internalization of decorin/collagen-coated beads decreased dose-dependently with increasing decorin concentration (p < 0.001). Inhibition of binding was sustained over 5 h (p < 0.001) and was attributed to interactions between decorin and collagen and not to decorin-collagen receptor interactions. Both the nonglycosylated decorin core protein and the thermally denatured decorin significantly inhibited collagen bead binding (ϳ50 and 89%, respectively; p < 0.05). Mimetic peptides corresponding to leucine-rich repeats 1-3, encompassed by a collagen-binding ϳ11-kDa cyanogen bromide fragment of decorin and leucine-rich repeats 4 and 5, previously shown to bind to collagen, were tested for their ability to inhibit collagen bead binding. Although the synthetic peptide 3 alone exhibited saturable binding to collagen, neither peptides 3 nor 1 and 2 markedly inhibited phagocytosis. Leucine-rich repeat 3 bound to a triple helical peptide containing the ␣2 integrin-binding site of collagen. When collagen beads were co-incubated with peptides 3 and 4, inhibition of collagen phagocytosis (55%) was equivalent to intact native/ recombinant core protein. Thus a novel collagen binding domain in decorin acts cooperatively with leucinerich repeat 4 to mask the ␣2␤1 integrin-binding site on collagen, an important sequence for the phagocytosis of collagen fibrils.The intracellular phagocytic pathway in fibroblasts contributes to the physiological remodeling of collagen by lysosomal degradation of internalized collagen fibrils (1-4), but the mechanisms that regulate this pathway in vivo are poorly characterized. Previous morphological studies have shown that collagen fibrils are "decorated" by proteoglycans (5); consequently, decorin may affect the binding step of collagen phagocytosis (6).Decorin (DCN) 1 is a matrix proteoglycan that belongs to the small leucine-rich proteoglycan family (7). The mature form of DCN (ϳ100 kDa) consists of an ϳ45-kDa core protein, a single dermatan or chondroitin sulfate glycosaminoglycan chain, cysteine loops near the N and C terminus, and either two or three asparagine-bound oligosaccharides. The central part of the core protein consists of 10 leucine-rich repeat (LRR) sequences in tandem array (8). Rotary shadowing-electron microscopy and molecular modeling studies suggest that the DCN core protein is horseshoe-shaped (9, 10) and that the inner concavity accommodates and may provide a binding site for type I collagen (10). Indeed, DCN binds not only to type I but also to collagen types II, III, VI,. DCN binding to collagen molecules is thought to influence collagen fi...

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Section: Discussionmentioning

confidence: 73%

Collagen Phagocytosis by Fibroblasts Is Regulated by Decorin

Bhide

Laschinger

Arora

et al. 2005

Journal of Biological Chemistry

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“…It co-localizes with large helical collagen fibers 15 and binds specific sites on collagen molecules as they assemble, thereby increasing the tensile strength of uncross-linked collagen fibers. 16 Decorin null mice have more severe LV dilation after experimentally-induced myocardial infarction. 17 In MR dogs, decorin mRNA downregulation correlated with the increase in LVEDD (Fig.…”

Section: Discussionmentioning

confidence: 99%

Microarray Identifies Extensive Downregulation of Noncollagen Extracellular Matrix and Profibrotic Growth Factor Genes in Chronic Isolated Mitral Regurgitation in the Dog

Chen²,

et al. 2009

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Background The volume overload of isolated mitral regurgitation (MR) in the dog results in left ventricular (LV) dilatation and interstitial collagen loss. To better understand the mechanism of collagen loss we performed a gene array and overlaid regulated genes into Ingenuity Pathway Analysis (IPA). Methods and Results Gene arrays from LV tissue were compared in 4 dogs prior to and 4 months after MR. Cine-magnetic resonance-derived LV end-diastolic volume increased 2-fold (p=0.005) and LV ejection fraction increased from 41 to 53% (p < 0.001). LV interstitial collagen decreased 40% (p<0.05) compared to controls and replacement collagen was in short strands and in disarray. IPA identified Marfan’s syndrome, aneurysm formation, LV dilatation, and myocardial infarction, all of which have extracellular matrix (ECM) protein defects and/or degradation. MMP-1 and -9 mRNA increased 5- (p=0.01) and 10-fold (0.003), while collagen I did not change and collagen III mRNA increased 1.5-fold (p=0.02). However, noncollagen genes important in ECM structure were significantly downregulated, including decorin, fibulin 1, and fibrillin 1. Decorin mRNA downregulation correlated with LV dilatation (r= 0.83 p<0.05). In addition, connective tissue growth factor and plasminogen activator inhibitor were downregulated, along with multiple genes in TGF-β signaling pathway, resulting decreased LV TGF-β1 activity (p=0.03). Conclusions LV collagen loss in isolated, compensated MR is chiefly due to post-translational processing and degradation. The downregulation of multiple noncollagen genes important in global ECM structure, coupled with decreased expression of multiple profibrotic factors, explain the failure to replace interstitial collagen in the MR heart.

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“…Several studies reported on the influence of SLRPs on collagen fibril formation in vitro . Decorin, for example, was shown to influence the fibrillogenesis rate as well as the diameter of collagen fibrils . While fibrillogenesis rate is thought to be mediated by both, the core protein as well as the chondroitin (CS)/dermatan sulfate chain in decorin, the regulation of the diameter was found to be particularly dependent on the glycosaminoglycan (GAG) part and its iduronic acid content …”

Section: Introductionmentioning

confidence: 99%

“…[5] Decorin, for example, was shown to influence the fibrillogenesis rate as well as the diameter of collagen fibrils. [9][10][11][12] While fibrillogenesis rate is thought to be mediated by both, the core protein as well as the chondroitin (CS)/dermatan sulfate chain in decorin, [9,12] the regulation of the diameter was found to be particularly dependent on the glycosaminoglycan (GAG) part and its iduronic acid content. [9,13] The influence of GAGs on the in vitro-fibrillogenesis of collagen has been studied since the 1960s.…”

Section: Introductionmentioning

confidence: 99%

Sulfated Hyaluronan Influences the Formation of Artificial Extracellular Matrices and the Adhesion of Osteogenic Cells

et al. 2014

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The aim of this study is to compare differentially sulfated hyaluronan (sHA) derivatives and chondroitin sulfate (CS) with respect to their ability to influence the formation of artificial extracellular matrices (aECMs) during in vitro-fibrillogenesis of collagen type I at high- and low-ionic strength. Analysis is performed using turbidity, biochemical assays, atomic force (AFM), and transmission electron microscopy (TEM). In general, high-sulfated glycosaminoglycans (GAGs) associate to a higher amount with collagen than the low-sulfated ones. The addition of GAGs prior to fibrillogenesis at low-ionic strength results in a dose-dependent decrease in fibril diameter. At high-ionic strength these effects are only obtained for the sHA derivatives but not for CS. Likewise, increasing concentrations and degree of GAG sulfation strongly affected the kinetics of fibrillogenesis. The impact of sulfation degree on F-actin location and fiber formation in SaOS-2 cells implies that adhesion-related intracellular signaling is influenced to a variable extent.

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Untitled

Cited by 42 publications

References 14 publications

Collagen Phagocytosis by Fibroblasts Is Regulated by Decorin

Collagen Phagocytosis by Fibroblasts Is Regulated by Decorin

Microarray Identifies Extensive Downregulation of Noncollagen Extracellular Matrix and Profibrotic Growth Factor Genes in Chronic Isolated Mitral Regurgitation in the Dog

Sulfated Hyaluronan Influences the Formation of Artificial Extracellular Matrices and the Adhesion of Osteogenic Cells

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