Disease relevance of DCN

• We report that bFGF upregulates the expression of the decorin gene in normal and keloid fibroblasts [1].
• In all analyzed cases, irrespective of the underlying disease, decorin and biglycan accumulated in glomeruli in areas of fibrous organization of the urinary space and in areas of tubulointerstitial fibrosis [2].
• Decorin accumulated in amyloid deposits, but not in deposits of fibrillary glomerulonephritis or immunotactoid glomerulopathy [2].
• Furthermore, decorin expression influences the expression of p21WAF1/CIP1, which has been related to kidney hypertrophy and hyperplasia [3].
• This study was conducted to monitor the time-course of expression of decorin in healing burn wounds by in-situ hybridization to determine whether its absence from hypertrophic scars could result from reduced synthesis [4].

Psychiatry related information on DCN

• Peripheral distribution of dermatan sulfate proteoglycans (decorin) in amyloid-containing plaques and their presence in neurofibrillary tangles of Alzheimer's disease [5].
• There is evidence indicating that these profibrotic factors interact with antifibrotic defense mechanisms, such as decrease of myofibroblast accumulation, elimination of reactive oxygen species by inducible nitric oxide synthase and neutralization of transforming-growth-factor beta1 by decorin, such that some plaques are in dynamic turnover [6].

High impact information on DCN

• On the basis of our results, decorin may eventually prove to be clinically useful in diseases associated with overproduction of TGF-beta [7].
• As transforming growth factor-beta induces synthesis of decorin in many cell types, our results suggest that decorin may be a component of a feedback system regulating cell growth [8].
• In studying the functional role of an extracellular matrix proteoglycan, decorin, we have made observations that suggest a role for this proteoglycan in the control of cell proliferation [9].
• The reduction in the saturation densities of the cell lines with the highest expression of decorin is more than 50% [9].
• We report here that Chinese hamster ovary (CHO) cell lines expressing human decorin from a stably transfected complementary DNA construct form a more orderly monolayer and grow to a lower saturation density than control cells lacking decorin [9].

Chemical compound and disease context of DCN

• Through its ability to bind extracellular matrix constituents and growth factors the small leucine-rich chondroitin/dermatan sulfate proteoglycan decorin which is present in many types of connective tissues may play an important biological role in remodeling and maintenance of extracellular matrices during inflammation, fibrosis, and cancer growth [10].
• Expression of decorin using the vaccinia virus/T7 expression system resulted in secretion of two distinct glycoforms: a proteoglycan substituted with a single chondroitin sulfate chain and N-linked oligosaccharides and a core protein glycoform substituted with N-linked glycans but without a glycosaminoglycan chain [11].
• Ectopic expression of decorin in C6 rat glioma cells results in strong inhibition of tumor formation in vivo [12].
• An increase in the length of the dermatan sulphate chain on decorin, a previously reported characteristic of this glycosaminoglycan in hypertrophic scar, was seen in all but two of the strains treated with transforming growth factor-beta 1 [13].
• TGF-beta antagonists, such as decorin, betaglycan, and possibly also heparin, might be potential candidates for future therapy to prevent diabetic vascular disease [14].

Biological context of DCN

• 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 [15].
• [125I]DCN poorly bound to subpeptide MKKTRG and did not bind at all to subpeptides VDAVRTEKGFLLLASLRQ and TLLALERKDHS, suggesting that heparin-binding sequence MKKTRG constituted a DCN binding site when flanked with peptides VDAVRTEKGFLLLASLRQ and TLLALERKDHS [16].
• Overall, these data indicate that modulation by steric exclusion of cell adhesion to a KKTR-dependent cell adhesive site present within the N-terminal domain of TSP could explain the antiadhesive properties of DCN [16].
• However, the mechanism by which decorin mediates its effect on cell proliferation is unclear [17].
• The effects of decorin persisted in the absence of extracellular Ca2+ but were blocked by AG1478, an epidermal growth factor (EGF)-specific tyrosine kinase inhibitor, and by down-regulation of the EGF receptor [17].

Anatomical context of DCN

• RESULTS: Chondroitin-6-sulphate and chondroitin-4-sulphate proteoglycan were increased in Turner syndrome fetuses and BGN seemed to be underexpressed compared with normal controls, while DCN was not [18].
• Decorin, a small multifunctional proteoglycan, is expressed by sprouting endothelial cells (ECs) during inflammation-induced angiogenesis in vivo and by human ECs co-cultured with fibroblasts in a collagen lattice [19].
• Interleukin (IL)-6 and IL-10 induce decorin mRNA in endothelial cells, but interaction with fibrillar collagen is essential for its translation [19].
• Two small interstitial dermatan sulfate-containing proteoglycans, biglycan and decorin, are present in extracellular matrices of skin, tendon, ligament, and cartilage [20].
• To investigate how decorin is induced, human EA.hy 926 ECs and/or human umbilical vein ECs were treated with interleukin (IL)-10 and IL-6 [19].

Associations of DCN with chemical compounds

• Decorin (DCN) is a ubiquitous proteoglycan comprised of a core protein attached to a single dermatan/chondroitin sulphate glycosaminoglycan chain [21].
• Northern blot analysis indicated that steady state messenger RNA (mRNA) concentration of DCN was increased by Dex in all of the HOB cultures and in seven of eight BMSC cultures analyzed [22].
• In addition, heparan sulfate drastically inhibited [125I]DCN binding to solid-phase adsorbed TSP (80% inhibition), suggesting that DCN could bind to the N-terminal domain of TSP through interaction with heparin-binding sequences [16].
• To address this question, a series of synthetic peptides, overlapping heparin-binding sequences ARKGSGRR (residues 22-29), KKTR (residues 80-83) and RLRIAKGGVNDN (residues 178-189), were synthesized and tested for their ability to interact with DCN [16].
• Several independent lines of evidence have implicated decorin, a small leucine-rich proteoglycan, in the inhibition of cell proliferation [17].

Physical interactions of DCN

• Decorin core protein fragment Leu155-Val260 interacts with TGF-beta but does not compete for decorin binding to type I collagen [23].
• Molecular mechanisms by which DCN interacts with TSP and inhibits cell adhesion to TSP are unknown [16].
• Leucine-rich repeat region of decorin binds to filamin-A [24].
• In support of this hypothesis saturable binding of TGF-beta1 and TGF-beta2 to collagen-bound native decorin could be demonstrated [23].
• In this study we provide evidence that decorin directly binds to the EGFR causing its dimerization, internalization, and ultimately its degradation [25].

Enzymatic interactions of DCN

• MMP-7 cleaves DCN into three major fragments which have the N-termini Asp1-Glu-Ala-Ser-Gly, Glu2-Ala-Ser-Gly-Ile and Leu244-His-Leu-Asp-Asn [21].

Regulatory relationships of DCN

• Decorin inhibits cell attachment to thrombospondin-1 by binding to a KKTR-dependent cell adhesive site present within the N-terminal domain of thrombospondin-1 [16].
• Gene expression profiles of LX-2 cells stimulated by TGF-beta1 in the presence and the absence of rhDecorin were obtained by using cDNA microarray technique and differentially expressed genes were identified to provide further insight into the molecular action mechanism of decorin on LX-2 cells [26].
• The growth factors did not affect the mRNA expression for biglycan, but they upregulated versican and downregulated decorin mRNA [27].
• Response to IL-10 by scleroderma fibroblasts was similar to that in normal dermal fibroblasts, with decreased expression levels of collagen and fibronectin and induced decorin mRNA levels [28].
• Decorin inhibits the epidermal growth factor receptor (EGFR) by down-regulating its tyrosine kinase activity, thereby blocking the growth of a variety of transformed cells and tumor xenografts [25].

Other interactions of DCN

• Both biglycan and decorin bound to type V collagen in a saturable and specific manner [20].
• Scatchard analysis showed that biglycan bound beta ig-h3 more avidly than decorin with Kd values estimated as 5.88 x 10(-8) and 1.02 x 10(-7) M, respectively [29].
• A remarkable finding was the observation that there was a reduction not only in the total levels of collagen, but also in osteonectin and three proteoglycans (a large chondroitin sulfate proteoglycan, biglycan, and decorin) [30].
• METHODS: Renal tissues from 18 patients with CGN were examined immunohistochemically for versican, decorin, biglycan and collagen type I, and were compared with morphologically normal tissues from six tumor nephrectomies [31].
• MMP-2 and MMP-3 digest DCN into seven major fragments in a similar pattern [21].

Analytical, diagnostic and therapeutic context of DCN

• This TGF-beta 1-elicited reduction was accompanied by an apparent increase in the size of the decorin molecules, although the size of the core protein was not altered, as judged by Western immunoblotting following chondroitinase ABC digestion [32].
• Recombinant human beta ig-h3 was found to bind 125I-labeled small leucine-rich proteoglycans (SLRPs), biglycan, and decorin, in co-immunoprecipitation experiments [29].
• Quantitation of both [35S]sulfate and [3H]leucine-labeled decorin in cell culture media by immunoprecipitation revealed a 50% reduction in decorin production in cell cultures treated with TGF-beta 1 [32].
• Decorin and biglycan mRNA synthesis was evaluated by in situ hybridization [2].
• Reverse transcriptase PCR (RT-PCR) confirmed that decorin mRNA levels are greatly elevated and also showed increased transcription of the TGF-beta 1 gene in hyperglycaemic cultures [33].

References