Biglycan is a novel binding partner of fibroblast growth factor receptor 3c (FGFR3c) in the human testis

Winge, Sofia B.; Nielsen, John; Jørgensen, Anne; Owczarek, Sylwia; Ewen, Katherine A.; Juul, Anders; Berezin, Vladimir; Meyts, Ewa Rajpert‐De

doi:10.1016/j.mce.2014.09.018

Cited by 14 publications

(12 citation statements)

References 38 publications

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“…Changes of the ECM are typical in testes of men with impairments of spermatogenesis. Especially fibrotic remodeling of the tubular wall occurs123 and, as indicated by a recent study, BGN is a major secreted proteoglycan derived from HTPCs131417. Interestingly, some of the CD68-positive macrophages identified in human testes were also positive for BGN, a result in line with rodent data1921.…”

Section: Discussionsupporting

confidence: 63%

“…Studies in nonhuman primate testes further indicate that testicular levels of DCN are inversely correlated to the sexual maturity16. BGN secreted by HTPCs was recently identified as a ligand of the spermatogonial stem cell receptor FGFR3c17. In addition a series of studies provide compelling evidence that it can also act as a ligand at Toll like receptors (TLRs), namely TLR2/4, expressed by macrophages.…”

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confidence: 99%

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Sterile inflammation as a factor in human male infertility: Involvement of Toll like receptor 2, biglycan and peritubular cells

Mayer¹,

Adam

Glashauser³

et al. 2016

Sci Rep

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Changes in the wall of seminiferous tubules in men with impaired spermatogenesis imply sterile inflammation of the testis. We tested the hypothesis that the cells forming the wall of seminiferous tubules, human testicular peritubular cells (HTPCs), orchestrate inflammatory events and that Toll like receptors (TLRs) and danger signals from the extracellular matrix (ECM) of this wall are involved. In cultured HTPCs we detected TLRs, including TLR2. A TLR-2 ligand (PAM) augmented interleukin 6 (IL-6), monocyte chemo-attractant protein-1 (MCP-1) and pentraxin 3 (PTX3) in HTPCs. The ECM-derived proteoglycan biglycan (BGN) is secreted by HTPCs and may be a TLR2-ligand at HTPCs. In support, recombinant human BGN increased PTX3, MCP-1 and IL-6 in HTPCs. Variable endogenous BGN levels in HTPCs derived from different men and differences in BGN levels in the tubular wall in infertile men were observed. In testes of a systemic mouse model for male infertility, testicular sterile inflammation and elevated estradiol (E2) levels, BGN was also elevated. Hence we studied the role of E2 in HTPCs and observed that E2 elevated the levels of BGN. The anti-estrogen ICI 182,780 blocked this action. We conclude that TLR2 and BGN contribute to sterile inflammation and infertility in man.

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Section: Discussionsupporting

confidence: 63%

mentioning

confidence: 99%

Sterile inflammation as a factor in human male infertility: Involvement of Toll like receptor 2, biglycan and peritubular cells

Mayer¹,

Adam

Glashauser³

et al. 2016

Sci Rep

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“…GO:0017134 concerns ‘fibroblast growth factor (FGF) binding’ ; FGFs are a family of growth factors, which play important roles in the processes of differentiation and proliferation of different tissues. The relationship between FGFs and testis has already been observed in [66]. …”

Section: Resultsmentioning

confidence: 77%

Identifying functional cancer-specific miRNA–mRNA interactions in testicular germ cell tumor

Sedaghat

Modarressi

Shojaie

2016

Journal of Theoretical Biology

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Testicular cancer is the most common cancer in men aged between 15 and 35 and more than 90% of testicular neoplasms are originated at germ cells. Recent research has shown the impact of microRNAs (miRNAs) in different types of cancer, including testicular germ cell tumor (TGCT). MicroRNAs are small non-coding RNAs which affect the development and progression of cancer cells by binding to mRNAs and regulating their expressions. The identification of functional miRNA-mRNA interactions in cancers, i.e. those that alter the expression of genes in cancer cells, can help delineate post-regulatory mechanisms and may lead to new treatments to control the progression of cancer. A number of sequence-based methods have been developed to predict miRNA-mRNA interactions based on the complementarity of sequences. While necessary, sequence complementarity is, however, not sufficient for presence of functional interactions. Alternative methods have thus been developed to refine the sequence-based interactions using concurrent expression profiles of miRNAs and mRNAs. This study aims to find functional cancer-specific miRNA-mRNA interactions in TGCT. To this end, the sequence-based predicted interactions are first refined using an ensemble learning method, based on two well-known methods of learning miRNA-mRNA interactions, namely, TaLasso and GenMiR++. Additional functional analyses were then used to identify a subset of interactions to be most likely functional and specific to TGCT. The final list of 13 miRNA-mRNA interactions can be potential targets for identifying TGCT-specific interactions and future laboratory experiments to develop new therapies.

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“…Although these findings suggest that biglycan exerts cardioprotective effects, the exact molecular mechanism behind this phenomenon has not yet been elucidated. Biglycan has been reported to bind to several cell membrane receptors including integrin receptors in lung fibroblast cells [69], growth factor receptors in human testis [70], Toll-like receptors (TLR) [53,71] and scavenger A receptors in macrophages [72]. Furthermore, TLR signaling induced by certain ligands has been shown to participate in cardioprotection [73,74].…”

Section: The Small Leucine-rich Proteoglycan Biglycanmentioning

confidence: 99%

“…Biglycan containing both the core protein and GAGs have already been reported to bind to several cell membrane receptors including integrin receptors [69], growth factor receptors [70], scavenger A receptors [72] and Toll-like receptors [53,71]. However, the role of these receptors in the cardiocytoprotective effect of biglycan has not been elucidated yet.…”

Section: Mechanisms Of Cardiocytoprotection Of Biglycan Core Proteinmentioning

confidence: 99%

Novel approaches of pharmacological preconditioning: the role of biglycan and miRNAs

Gáspár¹

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Biglycan is a novel binding partner of fibroblast growth factor receptor 3c (FGFR3c) in the human testis

Cited by 14 publications

References 38 publications

Sterile inflammation as a factor in human male infertility: Involvement of Toll like receptor 2, biglycan and peritubular cells

Sterile inflammation as a factor in human male infertility: Involvement of Toll like receptor 2, biglycan and peritubular cells

Identifying functional cancer-specific miRNA–mRNA interactions in testicular germ cell tumor

Novel approaches of pharmacological preconditioning: the role of biglycan and miRNAs

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