Disease relevance of Dcn

• Absence of decorin adversely influences tubulointerstitial fibrosis of the obstructed kidney by enhanced apoptosis and increased inflammatory reaction [1].
• We have therefore compared the development of tubulointerstitial kidney fibrosis in wild-type (WT) and decorin-/- mice in the model of unilateral ureteral obstruction [1].
• Up-regulation of decorin gene expression in the retinoic acid-treated mice might influence the pathogenesis of cleft palate [2].
• There is growing evidence that the two small leucine-rich proteoglycans biglycan and decorin regulate the assembly of connective tissues and alter cell behavior during development and pathological processes [3].
• What is the role of decorin in diabetic kidney disease [4]?
• We conclude that decorin is a natural protective factor against diabetic nephropathy and that the Dcn(-/-) diabetic mouse is a useful new model of progressive diabetic nephropathy [5].

High impact information on Dcn

• Toll-like receptors and T cell costimulatory molecules both trigger a DC survival pathway that is dependent on Bcl-x(L) [6].
• Thus, signals derived from the innate and acquired immune systems control DC lifespan and immunogenicity by distinct molecular mechanisms [6].
• To identify the genes that are differentially expressed upon maturation induced by exposure to Gram-negative bacteria, a kinetic study of DC gene expression was done with microarrays representing 11,000 genes and ESTs (expressed sequence tags) [7].
• Resistance to Lyme disease in decorin-deficient mice [8].
• A decorin-deficient (Dcn(-/-)) mouse was recently developed and found to have a relatively mild phenotype [8].

Chemical compound and disease context of Dcn

• Replication-deficient adenovirus was used to deliver decorin transgene (AdDec) to the airways by a single intranasal injection in a murine bleomycin model of lung fibrosis [9].
• Ectopic expression of the proteoglycan, decorin, abrogates the growth of experimental C6 gliomas in the rat [10].
• Adherence of Borrelia burgdorferi. Identification of critical lysine residues in DbpA required for decorin binding [11].

Biological context of Dcn

• However, already 12 hours after obstruction decorin-/- animals showed lower levels of p27(KIP1) and soon thereafter a more pronounced up-regulation and activation of initiator and effector caspases followed by enhanced apoptosis of tubular epithelial cells [1].
• In this study we investigated the role of decorin in TGF-beta-dependent inhibition of myogenesis [12].
• Using mice deficient in two members of the small leucine-rich proteoglycans, biglycan and decorin, we uncovered a role for these two extracellular matrix proteoglycans in modulating bone formation from bone marrow stromal cells [13].
• In the retinoic acid-treated mice, the area of the decorin gene expression expanded to the core region of the palate primordium where little signal was observed in control mice [2].
• The data suggest that differences in tissue distribution are responsible for the different effects on TGF-beta bioactivity in vivo, indicating that decorin, but not biglycan, has potential therapeutic value in fibrotic disorders of the lung [14].

Anatomical context of Dcn

• To probe the function of decorin during myogenesis, C(2)C(12) myoblasts were stably transfected with a plasmid expressing antisense decorin mRNA [12].
• Decorin is expressed during skeletal muscle differentiation and is up-regulated in dystrophic muscle [12].
• Thus, biglycan and decorin appear to be essential for maintaining an appropriate number of mature osteoblasts by modulating the proliferation and survival of bone marrow stromal cells [13].
• Osteopontin is consistently co-localized with calcified deposits, which progressively are transformed to psammoma bodies surrounded by decorin, especially in the right ventricle [15].
• A transient and dramatic up-regulation of biglycan was associated with newly formed myotubes, whereas decorin presented only minor variations [16].

Associations of Dcn with chemical compounds

• Decorin is a member of the family of the small leucine-rich proteoglycans [12].
• Decorin, a small dermatan-sulfate proteoglycan, participates in extracellular matrix assembly and influences directly and indirectly cell behavior via interactions with signaling membrane receptors and transforming growth factor (TGF)-beta [1].
• The resulting inhibition of decorin expression led to the expression of myogenin, a master transcription factor for muscle differentiation, under growth conditions and accelerated skeletal muscle differentiation as determined by the expression of creatine kinase [12].
• We evaluated biglycan and decorin expression in skeletal muscle during barium chloride-induced skeletal muscle regeneration in mice [16].
• Biglycan contains two chondroitin sulfate glycosaminoglycan (GAG) chains attached near its NH(2) terminus making it different from decorin that has only one GAG chain [17].

Physical interactions of Dcn

• Furthermore, decorin can bind IGF-I itself, but with a lower affinity (K(D) = 190 nm) than classical IGF-I-binding proteins [18].
• In wild type myoblasts, inhibition of decorin binding to LRP-1 and depletion of LRP-1 inhibited TGF-beta response to levels similar to those observed in Dcn null myoblasts [19].

Regulatory relationships of Dcn

• These findings strongly suggest a new role for decorin during skeletal muscle terminal differentiation by activating TGF-beta-dependent signaling pathways [12].
• In contrast myogenin expression was inhibited by adenovirally induced decorin expression or by adding exogenous decorin [12].
• In both models the IGF-I receptor was up-regulated in decorin-deficient mice compared with controls and the up-regulation could not compensate the decorin deficiency in the disease models [18].
• TIS10/PGS-2 antisense oligonucleotides also block production of PGE2 from endogenous arachidonate following endotoxin stimulation of both RAW 264.7 macrophage cells and murine peritoneal macrophages [20].
• Our findings indicate that further improvement in the healing of muscle lacerations is attained histologically by the combined administration of IGF-1 to enhance muscle regeneration and decorin to reduce the formation of fibrosis [21].

Other interactions of Dcn

• Chromatin immunoprecipitation assays further demonstrated that PBX proteins directly bind to the promoter of Bmp4 and Dcn in vivo in a RA-dependent fashion [22].
• In the old mice, calcified cartilage became enriched with regard to fibromodulin, while, in contrast, decorin deposition diminished, particularly near the tidemark [23].
• The interval mapping and test-cross results indicate that hg is not allelic with candidate genes Igf1 or decorin (Dcn), a gene that was mapped close to hg in this study [24].
• Asb4, Ata3, and Dcn are novel imprinted genes identified by high-throughput screening using RIKEN cDNA microarray [25].
• Especially the expression pattern of decorin and syndecan-3 coincided temporally and spatially exactly with that of OASIS [26].

Analytical, diagnostic and therapeutic context of Dcn

• Adenoviral gene transfer was used to overexpress active TGF-beta, decorin, and biglycan in cell culture and in murine lungs [14].
• Transmission electron microscopy analysis showed that like the decorin and biglycan knockouts, they have severely disturbed collagen fibril structures [17].
• In situ hybridization studies of developing mouse embryos showed a distinct pattern of expression with a progressive increase of decorin mRNA during ontogenesis [27].
• The physiological relevance of the decorin/IGF-I receptor interaction was corroborated in two animal models (e.g. inflammatory angiogenesis in the cornea and unilateral ureteral obstruction) [18].
• Immunofluorescence staining indicated a uniform expression of aggrecan, biglycan and decorin by all cells [28].

References