Disease relevance of Dcn

• On the other hand, albuminuria as a parameter of microvascular damage in hypertension and diabetes was ameliorated in fibrillin-1-underexpressing mice, possibly due to a compensatory upregulation of decorin [1].
• We report here that transfer of decorin cDNA into rat skeletal muscle increases the amount of decorin messenger RNA and protein present in skeletal muscle and decorin present in kidney, where it has a marked therapeutic effect on fibrosis induced by glomerulonephritis [2].
• The marked alterations of biglycan and decorin during the development of fibrosis suggests that these proteoglycans have a regulating role in this process [3].
• Expression of the proteoglycans biglycan and decorin and of transforming growth factor-beta 1 at various stages of liver fibrosis induced experimentally in rats by oral administration of thioacetamide was examined [4].
• Primary tumor growth in vivo was reduced by up to 67% upon decorin induction, and pulmonary metastases were markedly hampered as well [5].

High impact information on Dcn

• The proteoglycan decorin is a known inhibitor of TGF-beta1 [2].
• Gene therapy by skeletal muscle expression of decorin prevents fibrotic disease in rat kidney [2].
• Decorin mRNA, in contrast to biglycan decreased and reached 20% of control on day 10 [3].
• Since a reduction in C/EBP-beta expression does not affect the level of the ovulatory mediator prostaglandin endoperoxide synthase-2 (PGS-2), these findings support the view of C/EBP-beta as an important factor in the ovulatory process and highlight a C/EBP-beta-dependent and PGS-2-independent pathway that takes part in regulation of ovulation [6].
• In addition, the molecular packing structure of collagen shown here provides information concerning the potential modes of action of two prominent molecules involved in human health and disease: decorin and the Matrix Metallo-Proteinase (MMP) collagenase [7].

Chemical compound and disease context of Dcn

• The present findings suggest that decorin and thrombospondin-1 may participate in the development of tubulointerstitial fibrosis and may have some relation with TGF-beta1 in mercuric chloride-treated BN rats [8].

Biological context of Dcn

• We hypothesized that decorin binding to collagen inhibits phagocytosis of collagen fibrils [9].
• Results of nucleotide sequence analysis performed on these clones demonstrated that they encode the complete mature rat decorin protein expressed by VSMC [10].
• The vast majority of amino acid substitutions within rat decorin were of the conservative type [10].
• Molecular characterization of vascular smooth muscle decorin: deduced core protein structure and regulation of gene expression [10].
• Two overlapping clones containing sequences homologous to bovine, human and chicken decorin have been recovered from poly A+ RNA isolated from rat vascular smooth muscle cells (VSMC) using cDNA cloning and reverse transcription-polymerase chain reaction (PCR) methodologies [10].

Anatomical context of Dcn

• Tissue sections were incubated with antibodies to the small, leucine-rich PG, decorin, and biglycan and collagen type I. Airways were classified according to basement membrane perimeter length (< or =0.99, 1-2.99, and > or =3 mm) [11].
• Collagen phagocytosis by fibroblasts is regulated by decorin [9].
• Complexes of matrilin-1 and biglycan or decorin connect collagen VI microfibrils to both collagen II and aggrecan [12].
• The amount of DSPG per cervix increases 4-fold during pregnancy, then falls precipitously within 1 day post partum [13].
• A cDNA clone for dermatan sulfate proteoglycan-II, or decorin, has been isolated from a rat uterus library and sequenced [14].

Associations of Dcn with chemical compounds

• Thus a novel collagen binding domain in decorin acts cooperatively with leucine-rich repeat 4 to mask the alpha2beta1 integrin-binding site on collagen, an important sequence for the phagocytosis of collagen fibrils [9].
• The expression of genes encoding the core proteins of the novel small chondroitin/dermatan sulfate proteoglycans decorin and biglycan was studied in the livers of normal rats and in liver tissue during fibrogenesis induced by prolonged bile-duct ligation and thioacetamide poisoning [15].
• In addition, we have shown that another chondroitin sulfate-containing protein, decorin, will also form a complex with the heavy chain, as will free chondroitin sulfate chains [16].
• Expression of extracellular matrix proteoglycans perlecan and decorin in carbon-tetrachloride-injured rat liver and in isolated liver cells [17].
• The LH surge induces ovulation [prostaglandin synthase-2 (PGS-2)] and luteinization (progesterone synthesis) of preovulatory follicles by cAMP-dependent mechanisms [18].

Regulatory relationships of Dcn

• In addition to pharmacological induction by TPA + A23187, TIS10/PGS-2 message is also induced by the inflammatory cytokine interleukin 1-beta (IL-1 beta) [19].
• Decorin is a protein composed of a core protein and a chondroitin sulfate side chain and is capable of inactivating TGF-beta [20].
• Ex vivo transfer of the decorin gene into rat glomerulus via a mesangial cell vector suppressed extracellular matrix accumulation in experimental glomerulonephritis [21].

Other interactions of Dcn

• Northern blot, RT-PCR, Western blot, and promoter activity assays revealed that HGF caused a significant increase in decorin mRNA and protein, as well as in biglycan mRNA, protein, and promoter activity, suggesting transcriptional control of gene expression [22].
• TGF-beta does, however, augment both induced prostacyclin accumulation and the induced synthesis and accumulation of TIS10/PGS-2 protein and message in IEC-6 cells [19].
• RT-PCR analysis showed that versican mRNA was highly expressed at P1 but was little expressed at P42. mRNAs for other chondroitin sulfate proteoglycans including biglycan, aggrecan, and decorin did not change much between P1 and P42 [23].
• Moreover, decorin and thrombospondin-1 proteins were localized in tubular epithelial cells and peritubular interstitium [8].
• Chronic liver damage was characterized by the deposition of decorin and perlecan in the fibrotic septa [17].

Analytical, diagnostic and therapeutic context of Dcn

• A small dermatan sulphate proteoglycan (DSPG) was extracted from rat cervices and was purified by using DEAE-Sephacel ion-exchange chromatography, gel filtration on Sepharose CL-2B and CsCl-density-gradient centrifugation [13].
• The main induced proteoglycans were identified as biglycan and decorin by immunoprecipitation with antiserum made against synthetic peptides from the proteoglycan core proteins [24].
• Spatial and temporal patterns of gene expression for the proteoglycans biglycan and decorin and for transforming growth factor-beta 1 revealed by in situ hybridization during experimentally induced liver fibrosis in the rat [4].
• Immunoelectron microscopy revealed decorin to be abundantly localized in the vicinity of the collagen fibrils [25].
• Decorin, a transforming growth factor-beta-inhibiting proteoglycan, reduced collagen content but did not affect net ultrafiltration [26].

References