The cytoprotective effect of biglycan core protein involves Toll-like receptor 4 signaling in cardiomyocytes

Gáspár, Renáta; Pipicz, Márton; Hawchar, Fatime; Kovács, Dóra; Djirackor, Luna; Görbe, Anikó; Varga, Zoltán V.; Kiricsi, Mónika; Petrovski, Goran; Gácser, Attila; Csonka, Csaba; Csont, Tamás

doi:10.1016/j.yjmcc.2016.08.006

Cited by 25 publications

(34 citation statements)

References 49 publications

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“…Other knockout SLRP models, including biglycan, decorin, and double biglycan and fibromodulin, have varying degrees of apparent phenotypes including accelerated degeneration of articular cartilage, subchondral sclerosis, reduced growth rate of bone with decreased bone mass, and disruption of proper collagen fibrillogenesis [ 47 – 50 ]. Conversely, supplementation of SLRPs provides evidence for crucial roles in: signaling pathways, such as the TGF-β (transforming growth factor beta), WNT , TLR (toll-like receptor), EGFR (epithelial growth factor receptor) internalization, and Akt -dependant/−independent; collagenase shielding; collagen fibrillogenesis in the form of wound healing and scar mitigation; and proteoglycan regulation [ 26 , 50 – 59 ].…”

Section: Discussionmentioning

confidence: 99%

Adding exogenous biglycan or decorin improves tendon formation for equine peritenon and tendon proper cells in vitro

Pechanec

Boyd

Baar

et al. 2020

BMC Musculoskelet Disord

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Background Tendon injuries amount to one of the leading causes of career-ending injuries in horses due to the inability for tendon to completely repair and the high reinjury potential. As a result, novel therapeutics are necessary to improve repair with the goal of decreasing leg lameness and potential reinjury. Small leucine-rich repeat proteoglycans (SLRPs), a class of regulatory molecules responsible for collagen organization and maturation, may be one such therapeutic to improve tendon repair. Before SLRP supplementation can occur in vivo, proper evaluation of the effect of these molecules in vitro needs to be assessed. The objective of this study was to evaluate the effectiveness of purified bovine biglycan or decorin on tendon proper and peritenon cell populations in three-dimensional tendon constructs. Methods Equine tendon proper or peritenon cell seeded fibrin three-dimensional constructs were supplemented with biglycan or decorin at two concentrations (5 nM or 25 nM). The functionality and ultrastructural morphology of the constructs were assessed using biomechanics, collagen content analysis, transmission electron microscopy (TEM), and gene expression by real time – quantitative polymerase chain reaction (RT-qPCR). Results SLRP supplementation affected both tendon proper and peritenon cells-seeded constructs. With additional SLRPs, material and tensile properties of constructs strengthened, though ultrastructural analyses indicated production of similar-sized or smaller fibrils. Overall expression of tendon markers was bolstered more in peritenon cells supplemented with either SLRP, while supplementation of SLRPs to TP cell-derived constructs demonstrated fewer changes in tendon and extracellular matrix markers. Moreover, relative to non-supplemented tendon proper cell-seeded constructs, SLRP supplementation of the peritenon cells showed increases in mechanical strength, material properties, and collagen content. Conclusions The SLRP-supplemented peritenon cells produced constructs with greater mechanical and material properties than tendon proper seeded constructs, as well as increased expression of matrix assembly molecules. These findings provide evidence that SLRPs should be further investigated for their potential to improve tendon formation in engineered grafts or post-injury.

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Section: Discussionmentioning

confidence: 99%

Adding exogenous biglycan or decorin improves tendon formation for equine peritenon and tendon proper cells in vitro

Pechanec

Boyd

Baar

et al. 2020

BMC Musculoskelet Disord

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“…That BGN overexpression was particularly linked to PTEN deletions is of interest with respect to previous reports linking class I proteoglycans – including BGN — to several growth pathways including AKT signaling [2] , [31] ). For example, earlier work demonstrates that excess extracellular matrix concentrations of soluble BGN can induce cell growth and survival via activation of multiple growth factor receptors including the AKT-upstream receptor EGFR [31] , [59] . That activated AKT is also required for BGN core protein synthesis [33] is seen as further support for a role of BGN in signal regulation networks [2] , and might also provide an explanation for the marked up-regulation of BGN in PTEN-deleted and AKT-hyperactivated cancers.…”

Section: Discussionmentioning

confidence: 99%

Up-regulation of Biglycan is Associated with Poor Prognosis and PTEN Deletion in Patients with Prostate Cancer

et al. 2017

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Biglycan (BGN), a proteoglycan of the extracellular matrix, is included in mRNA signatures for prostate cancer aggressiveness. To understand the impact of BGN on prognosis and its relationship to molecularly defined subsets, we analyzed BGN expression by immunohistochemistry on a tissue microarray containing 12,427 prostate cancers. Seventy-eight percent of 11,050 interpretable cancers showed BGN expression, which was considered as low intensity in 47.7% and as high intensity in 31.1% of cancers. BGN protein expression rose with increasing pathological tumor stage, Gleason grade, lymph node metastasis and early PSA recurrence (P < .0001 each). Comparison with our molecular database attached to the TMA revealed that BGN expression was linked to presence of TMPRRS2:ERG fusion and PTEN deletion (P < .0001 each). In addition, BGN was strongly linked to androgen-receptor (AR) levels (P < .0001), suggesting a hormone-depending regulation of BGN. BGN up-regulation is a frequent feature of prostate cancer that parallels tumor progression and may be useful to estimate tumor aggressiveness particularly if combined with other molecular markers.

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“…On the other hand, various in vitro and in vivo studies have shown that the stimulation of TLRs (mainly TLR2 and TLR4, which are localized on both tumor cells and tumor‐associated host cells) leads to an increase in the survival, proliferation and metastatic potential of tumor cells . In contrast to HA or heparan sulfate, CS is not a typical ligand for TLR2 and TLR4 . However, there is some evidence that CS can interact with and affect TLR function.…”

Section: The Role Of C‐6‐s In the Tumor Nichementioning

confidence: 99%

The dual role of the glycosaminoglycan chondroitin‐6‐sulfate in the development, progression and metastasis of cancer

et al. 2019

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The remarkable structural heterogeneity of chondroitin sulfate (CS) and dermatan sulfate (DS) generates biological information that can be unique to each of these glycosaminoglycans (GAGs), and changes in their composition are translated into alterations in the binding profiles of these molecules. CS/DS can bind to various cytokines and growth factors, cell surface receptors, adhesion molecules, enzymes and fibrillar glycoproteins of the extracellular matrix, thereby influencing both cell behavior and the biomechanical and biochemical properties of the matrix. In this review, we summarize the current knowledge concerning CS/DS metabolism in the human cancer stroma. The remodeling of the GAG profile in the tumor niche is manifested as a substantial increase in the CS content and a gradual decrease in the proportion between DS and CS. Furthermore, the composition of CS and DS is also affected, which results in a substantial increase in the 6‐O‐sulfated and/or unsulfated disaccharide content, which is concomitant with a decrease in the 4‐O‐sulfation level. Here, we discuss the possible impact of alterations in the CS/DS sulfation pattern on the binding capacity and specificity of these GAGs. Moreover, we propose potential consequences of the stromal accumulation of chondroitin‐6‐sulfate for the progression and metastasis of cancer.

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The cytoprotective effect of biglycan core protein involves Toll-like receptor 4 signaling in cardiomyocytes

Cited by 25 publications

References 49 publications

Adding exogenous biglycan or decorin improves tendon formation for equine peritenon and tendon proper cells in vitro

Adding exogenous biglycan or decorin improves tendon formation for equine peritenon and tendon proper cells in vitro

Up-regulation of Biglycan is Associated with Poor Prognosis and PTEN Deletion in Patients with Prostate Cancer

The dual role of the glycosaminoglycan chondroitin‐6‐sulfate in the development, progression and metastasis of cancer

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