Disease relevance of BGN

• Overexpression of the small leucine-rich proteoglycan biglycan (BGN) in fibrosis and desmoplasia results from enhanced activity of transforming growth factor-beta (TGF-beta) [1].
• In pancreatic adenocarcinoma, the tumor cells themselves may contribute to BGN synthesis in vivo, since 8 of 18 different pancreatic carcinoma cell lines constitutively expressed BGN mRNA, as shown by reverse transcription-PCR analysis [1].
• A dysregulation in BGN expression occurs under several pathological conditions, including glomerulonephritis, mesothelioma, pancreatic cancer and a mouse model of osteoporosis [2].
• We have initiated studies of structural and functional domains of biglycan by transient eukaryotic expression using the vaccinia virus/T7 bacteriophage expression system [3].
• A recombinant vaccinia virus, vBGN4 encoding the mature biglycan core protein as a polyhistidine fusion protein under control of the T7 phage promoter was expressed in HT-1080 cells and UMR106 cells [3].

Psychiatry related information on BGN

• ABG was associated with age, alcohol consumption and PGI/PGII<3 [4].
• The subjects were also rated on the Brief Psychiatric Rating Scale, Pierce's Suicide Intent Scale, the Superego Paranoia Depression Scale, the Hostility and Direction of Hostility Questionnaire, the PGI Locus of Control Scale and the Alienation Scale [5].
• Neuropsychological parameters of general intelligence (Malin's modification of WISC test); attention and concentration (colour cancellation test); memory (modified PGI memory test) and visuomotor perception (Bender Gestalt test) were evaluated at least 6 months after CNS prophylaxis [6].

High impact information on BGN

• Four markers at Xq28 were analyzed (DXS1113, BGN, Factor 8, and DXS1108) [7].
• In this study, we identified Biglycan (Bgn), a member of the small leucine-rich proteoglycan family, as a new extracellular modulator of BMP4 signaling [8].
• We have investigated the expression patterns and subcellular localization in nervous tissue of glypican, a major glycosylphosphatidylinositol-anchored heparan sulfate proteoglycan that is predominantly synthesized by neurons, and of biglycan, a small, leucine-rich chondroitin sulfate proteoglycan [9].
• In certain regions, staining was selective, insofar as glypican and biglycan immunoreactivity in the nucleus was seen predominantly in a subpopulation of large spinal cord neurons [9].
• By laser scanning confocal microscopy of rat central nervous tissue and C6 glioma cells, we found that a significant portion of the glypican and biglycan immunoreactivity colocalized with nuclear staining by propidium iodide and was also seen in isolated nuclei [9].

Chemical compound and disease context of BGN

• Aberrant expressions of decorin and biglycan genes in the carbohydrate-deficient glycoprotein syndrome [10].
• In addition, the combination of biglycan overexpression and Ang II infusion resulted in marked increases in vascular smooth muscle cell proliferation and migration in the coronary arteries, as well as increases in fibrosis surrounding the vessels [11].
• The content of decorin in hypertrophic scars was only 25% of that in normal skin whereas the large chondroitin sulphate proteoglycan and biglycan were each about 6-fold higher [12].
• IL-1 may be a necessary mediator of increased circulating PGI, TXB2, LTC4D4E4, and IL-6 levels in patients with sepsis syndrome [13].
• In contrast, iduronic acid-containing proteoglycans from hypertrophic scar were found to be approximately 30% biglycan [PG(IdoA)-I] [14].

Biological context of BGN

• Ectopic expression of a dominant-negative mutant of the TGF-beta type II receptor in PANC-1 cells abrogated TGF-beta-induced BGN up-regulation [15].
• Regional localization of BGN to Xq13-qter and DCN to 12p12.1-qter was also obtained by examining hybrids containing spontaneous breaks or well-characterized translocations involving chromosomes X and 12 [16].
• Western and immunohistochemical analysis revealed that absence of a second X chromosome, as is the case in Turner syndrome, affects BGN protein pattern [17].
• Since the extracellular concentration of BGN is regulated both by secretion and endocytosis, we performed mechanistic studies on BGN endocytosis in human skin fibroblasts in vitro, using inhibitors of different endocytic routes [2].
• Adhesion and Rac1-dependent regulation of biglycan gene expression by transforming growth factor-beta. Evidence for oxidative signaling through NADPH oxidase [18].

Anatomical context of BGN

• Biglycan was expressed by glomerular endothelial cells and, together with fibromodulin, by distal tubular cells and in collecting ducts [19].
• Two small interstitial dermatan sulfate-containing proteoglycans, biglycan and decorin, are present in extracellular matrices of skin, tendon, ligament, and cartilage [20].
• The effect of glucocorticoid on the synthesis of biglycan and decorin in human osteoblasts and bone marrow stromal cells [21].
• Decorin and versican, but not biglycan, were increased in the hyperglycaemic mesangial cell culture media [22].
• Biglycan, but not decorin, accumulated in the neointima of arteriosclerotic blood vessels [23].

Associations of BGN with chemical compounds

• The steady state mRNA level of BGN was decreased by Dex in both HOB and BMSC cultures [21].
• The relationship of biglycan to a number of other proteins containing the leucine-rich repeats is discussed with respect to homologies of cysteine regions immediately adjacent to the repeat sequences [24].
• Approximately 70% of the recombinant biglycan secreted by HT-1080 cells was substituted with chondroitin sulfate chains, whereas about 50% of the biglycan expressed by UMR106 cells was substituted with chondroitin sulfate chains [3].
• We investigated the effects of biglycan and decorin on the inhibition of alpha-thrombin by the serine proteinase inhibitor heparin cofactor II [20].
• However, when the secondary structure of recombinant biglycan was disrupted by exposure to 4 M guanidine hydrochloride, the affinity for collagen type V was dramatically reduced [3].

Physical interactions of BGN

• Biglycan core protein was shown to inhibit the extent of complexing of beta ig-h3 with native and pepsin-collagen VI suggesting that the glycosaminoglycan side chains of the proteoglycan were important for the formation of the large ternary complexes [25].
• BACKGROUND: The small interstitial proteoglycans decorin and biglycan have been shown to interact with various extracellular matrix molecules and with transforming growth factor-beta [26].
• Domains of apolipoprotein E involved in the binding to the protein core of biglycan of the vascular extracellular matrix: potential relationship between retention and anti-atherogenic properties of this apolipoprotein [27].
• LPL had a slightly greater effect on increasing the binding of native and oxidized LDL to biglycan than versican [28].
• Both types of adiponectin bound to biglycan in a dose-dependent manner [29].

Co-localisations of BGN

• Versican colocalized with biglycan [30].

Regulatory relationships of BGN

• Decorin production was inhibited by about 34% by all treatments, while biglycan was upregulated 1.3-fold by TNF-alpha [31].
• Decorin was expressed later than biglycan, was associated with early matrix deposition, but then continued to the mineralisation stages [32].
• IL-6 up-regulated biglycan expression, but less strongly than TGF-beta3 [33].
• Decorin and biglycan were found not to inhibit the interaction of pepsin-treated type VI collagen with MAGP-1, indicating that its binding site on the collagen is not close to that for the proteoglycans [34].

Other interactions of BGN

• Both biglycan and decorin bound to type V collagen in a saturable and specific manner [20].
• Analysis of 35S-labeled proteoglycans in the culture media of skin and gingival fibroblasts also revealed stimulation of biglycan and versican production, and reduction in decorin production [35].
• Co-immunoprecipitation of 125I-labeled biglycan incubated with equimolar mixtures of beta ig-h3 and pepsin-collagen VI was increased 6-fold over beta ig-h3 alone and 3-fold over collagen VI alone [25].
• Smad4/DPC4-dependent regulation of biglycan gene expression by transforming growth factor-beta in pancreatic tumor cells [1].
• Biglycan was expressed by glomerular endothelial cells and, together with fibromodulin, was synthesized and deposited in distal tubular cells and collecting ducts [36].

Analytical, diagnostic and therapeutic context of BGN

• Recombinant human beta ig-h3 was found to bind 125I-labeled small leucine-rich proteoglycans (SLRPs), biglycan, and decorin, in co-immunoprecipitation experiments [25].
• This was confirmed by electron microscopy after negative staining of complexes between gold-labeled proteoglycans and collagen VI, demonstrating that both biglycan and decorin bound exclusively to a domain close to the interface between the N terminus of the triple helical region and the following globular domain [37].
• The binding of native biglycan and decorin to pepsin-extracted collagen VI from human placenta was examined by solid phase assay and by measurement of surface plasmon resonance in the BIAcore(TM)2000 system [37].
• RESULTS: Two bands of decorin and a single band of biglycan mRNA were identified in Northern blots of isolated glomeruli [36].
• Decorin and biglycan mRNA synthesis was evaluated by in situ hybridization [23].

References