Decorin Explained

Decorin is a protein that in humans is encoded by the DCN gene.

Decorin is a proteoglycan that is on average 90 - 140 kilodaltons (kDa) in molecular weight. It belongs to the small leucine-rich proteoglycan (SLRP) family and consists of a protein core containing leucine repeats with a glycosaminoglycan (GAG) chain consisting of either chondroitin sulfate (CS) or dermatan sulfate (DS).

Decorin is a small cellular or pericellular matrix proteoglycan and is closely related in structure to biglycan protein. Decorin and biglycan are thought to be the result of a gene duplication. This protein is a component of connective tissue, binds to type I collagen fibrils, and plays a role in matrix assembly.^[1]

Naming

Decorin's name is a derivative of both the fact that it "decorates" collagen type I, and that it interacts with the "d" and "e" bands of fibrils of this collagen.

Function

Decorin appears to influence fibrillogenesis, and also interacts with fibronectin, thrombospondin, the complement component C1q, epidermal growth factor receptor (EGFR) and transforming growth factor-beta (TGF-beta).

Decorin has been shown to either enhance or inhibit the activity of TGF-beta 1. The primary function of decorin involves regulation during the cell cycle.

It has been involved in the regulation of autophagy, of endothelial cell and inhibits angiogenesis. This process is mediated by a high-affinity interaction with VEGFR2 (vascular endothelial growth factor receptor) which leads to increased levels of tumor suppressor gene called PEG3.^[2] Other angiogenic growth factors that decorin inhibits are angiopoietin, hepatocyte growth factor (HGF) and platelet-derived growth factor (PDGF).^[3]

Decorin has recently been established as a myokine. In this role, it promotes muscle hypertrophy by binding with myostatin.^[4]

Clinical significance

Keloid scars have decreased decorin expression compared to healthy skin.^[5] Development of congenital stromal corneal dystrophy is dependent on export and extracellular deposition of truncated decorin. ^[6]

Animal studies

Infusion of decorin into experimental rodent spinal cord injuries has been shown to suppress scar formation and promote axon growth.

Decorin has been shown to have anti-tumorigenic properties in an experimental murine tumor model and is capable of suppressing the growth of various tumor cell lines. ^[7] The decorin-deficient knockout mouse shows reduced inflammatory reactions during contact dermatitis due to a defect in leukocyte recruitment and altered interferon gamma function. ^{[8] [9]}

Interactions

Decorin has been shown to interact with:

• Collagen type I^[10]
• Epidermal growth factor receptor^{[11] [12]} and
• TGF beta 1,^{[13] [14]}
• TLR2,^[15] and
• TLR4.^[15]

Further reading

• Ständer M, Naumann U, Wick W, Weller M . Transforming growth factor-beta and p-21: multiple molecular targets of decorin-mediated suppression of neoplastic growth . Cell and Tissue Research . 296 . 2 . 221–7 . May 1999 . 10382266 . 10.1007/s004410051283 . 20282995 .
• Fujisawa R . [Recent advances in research on bone matrix proteins] . Nihon Rinsho. Japanese Journal of Clinical Medicine . 60 . 72–8 . March 2002 . Suppl 3 . 11979972 .
• Krumdieck R, Höök M, Rosenberg LC, Volanakis JE . The proteoglycan decorin binds C1q and inhibits the activity of the C1 complex . Journal of Immunology . 149 . 11 . 3695–701 . December 1992 . 10.4049/jimmunol.149.11.3695 . 1431141 . 23005992 . free .
• Winnemöller M, Schön P, Vischer P, Kresse H . Interactions between thrombospondin and the small proteoglycan decorin: interference with cell attachment . European Journal of Cell Biology . 59 . 1 . 47–55 . October 1992 . 1468447 .
• Murphy-Ullrich JE, Schultz-Cherry S, Höök M . Transforming growth factor-beta complexes with thrombospondin . Molecular Biology of the Cell . 3 . 2 . 181–8 . February 1992 . 1550960 . 275517 . 10.1091/mbc.3.2.181 .
• Pulkkinen L, Alitalo T, Krusius T, Peltonen L . Expression of decorin in human tissues and cell lines and defined chromosomal assignment of the gene locus (DCN) . Cytogenetics and Cell Genetics . 60 . 2 . 107–11 . 1992 . 1611907 . 10.1159/000133314 .
• McBride OW, Fisher LW, Young MF . Localization of PGI (biglycan, BGN) and PGII (decorin, DCN, PG-40) genes on human chromosomes Xq13-qter and 12q, respectively . Genomics . 6 . 2 . 219–25 . February 1990 . 1968422 . 10.1016/0888-7543(90)90560-H .
• Fleischmajer R, Fisher LW, MacDonald ED, Jacobs L, Perlish JS, Termine JD . Decorin interacts with fibrillar collagen of embryonic and adult human skin . Journal of Structural Biology . 106 . 1 . 82–90 . February 1991 . 2059554 . 10.1016/1047-8477(91)90065-5 .
• Pulkkinen L, Kainulainen K, Krusius T, Mäkinen P, Schollin J, Gustavsson KH, Peltonen L . Deficient expression of the gene coding for decorin in a lethal form of Marfan syndrome . The Journal of Biological Chemistry . 265 . 29 . 17780–5 . October 1990 . 10.1016/S0021-9258(18)38231-0 . 2211661 . free .
• Yamaguchi Y, Mann DM, Ruoslahti E . Negative regulation of transforming growth factor-beta by the proteoglycan decorin . Nature . 346 . 6281 . 281–4 . July 1990 . 2374594 . 10.1038/346281a0 . 1990Natur.346..281Y . 4272333 .
• Greve H, Blumberg P, Schmidt G, Schlumberger W, Rauterberg J, Kresse H . Influence of collagen lattice on the metabolism of small proteoglycan II by cultured fibroblasts . The Biochemical Journal . 269 . 1 . 149–55 . July 1990 . 2375748 . 1131544 . 10.1042/bj2690149 .
• Roughley PJ, White RJ . Dermatan sulphate proteoglycans of human articular cartilage. The properties of dermatan sulphate proteoglycans I and II . The Biochemical Journal . 262 . 3 . 823–7 . September 1989 . 2590169 . 1133347 . 10.1042/bj2620823 .
• Fisher LW, Termine JD, Young MF . Deduced protein sequence of bone small proteoglycan I (biglycan) shows homology with proteoglycan II (decorin) and several nonconnective tissue proteins in a variety of species . The Journal of Biological Chemistry . 264 . 8 . 4571–6 . March 1989 . 10.1016/S0021-9258(18)83781-4 . 2647739 . free .
• Yamaguchi Y, Ruoslahti E . Expression of human proteoglycan in Chinese hamster ovary cells inhibits cell proliferation . Nature . 336 . 6196 . 244–6 . November 1988 . 3194009 . 10.1038/336244a0 . 1988Natur.336..244Y . 4338095 .
• Krusius T, Ruoslahti E . Primary structure of an extracellular matrix proteoglycan core protein deduced from cloned cDNA . Proceedings of the National Academy of Sciences of the United States of America . 83 . 20 . 7683–7 . October 1986 . 3484330 . 386785 . 10.1073/pnas.83.20.7683 . 1986PNAS...83.7683K . free .
• Fisher LW, Hawkins GR, Tuross N, Termine JD . Purification and partial characterization of small proteoglycans I and II, bone sialoproteins I and II, and osteonectin from the mineral compartment of developing human bone . The Journal of Biological Chemistry . 262 . 20 . 9702–8 . July 1987 . 10.1016/S0021-9258(18)47991-4 . 3597437 . free .
• Lysiak JJ, Hunt J, Pringle GA, Lala PK . Localization of transforming growth factor beta and its natural inhibitor decorin in the human placenta and decidua throughout gestation . Placenta . 16 . 3 . 221–31 . April 1995 . 7638106 . 10.1016/0143-4004(95)90110-8 .
• Takeuchi Y, Kodama Y, Matsumoto T . Bone matrix decorin binds transforming growth factor-beta and enhances its bioactivity . The Journal of Biological Chemistry . 269 . 51 . 32634–8 . December 1994 . 10.1016/S0021-9258(18)31681-8 . 7798269 . free .
• Scholzen T, Solursh M, Suzuki S, Reiter R, Morgan JL, Buchberg AM, Siracusa LD, Iozzo RV . 6 . The murine decorin. Complete cDNA cloning, genomic organization, chromosomal assignment, and expression during organogenesis and tissue differentiation . The Journal of Biological Chemistry . 269 . 45 . 28270–81 . November 1994 . 10.1016/S0021-9258(18)46924-4 . 7961765 . free .
• Danielson KG, Fazzio A, Cohen I, Cannizzaro LA, Eichstetter I, Iozzo RV . The human decorin gene: intron-exon organization, discovery of two alternatively spliced exons in the 5' untranslated region, and mapping of the gene to chromosome 12q23 . Genomics . 15 . 1 . 146–60 . January 1993 . 8432526 . 10.1006/geno.1993.1022 .
• Bredrup C, Knappskog PM, Majewski J, Rødahl E, Boman H . Congenital stromal dystrophy of the cornea caused by a mutation in the decorin gene . Investigative Ophthalmology & Visual Science . 46 . 2 . 420–6 . February 2005 . 15671264 . 10.1167/iovs.04-0804 .

External links

• GeneReviews/NCBI/NIH/UW entry on Congenital Stromal Corneal Dystrophy

Notes and References

1. Web site: Entrez Gene: DCN decorin.
2. Buraschi S, Neill T, Goyal A, Poluzzi C, Smythies J, Owens RT, Schaefer L, Torres A, Iozzo RV . 6 . Decorin causes autophagy in endothelial cells via Peg3 . Proceedings of the National Academy of Sciences of the United States of America . 110 . 28 . E2582-91 . July 2013 . 23798385 . 3710796 . 10.1073/pnas.1305732110 . 2013PNAS..110E2582B . free .
3. Järveläinen H, Sainio A, Wight TN . Pivotal role for decorin in angiogenesis . Matrix Biology . 43 . 15–26 . April 2015 . 25661523 . 4560244 . 10.1016/j.matbio.2015.01.023 .
4. Kanzleiter T, Rath M, Görgens SW, Jensen J, Tangen DS, Kolnes AJ, Kolnes KJ, Lee S, Eckel J, Schürmann A, Eckardt K . 6 . The myokine decorin is regulated by contraction and involved in muscle hypertrophy . Biochemical and Biophysical Research Communications . 450 . 2 . 1089–94 . July 2014 . 24996176 . 10.1016/j.bbrc.2014.06.123 .
5. Jumper N, Paus R, Bayat A . Functional histopathology of keloid disease . Histology and Histopathology . 30 . 9 . 1033–57 . September 2015 . 25900252 . 10.14670/HH-11-624 .
6. Mellgren AE, Bruland O, Vedeler A, Saraste J, Schönheit J, Bredrup C, Knappskog PM, Rødahl E . 6 . Development of congenital stromal corneal dystrophy is dependent on export and extracellular deposition of truncated decorin . Investigative Ophthalmology & Visual Science . 56 . 5 . 2909–15 . May 2015 . 26029887 . 10.1167/iovs.14-16014 .
7. Sofeu Feugaing DD, Götte M, Viola M . More than matrix: the multifaceted role of decorin in cancer . European Journal of Cell Biology . 92 . 1 . 1–11 . January 2013 . 23058688 . 10.1016/j.ejcb.2012.08.004 .
8. Seidler DG, Mohamed NA, Bocian C, Stadtmann A, Hermann S, Schäfers K, Schäfers M, Iozzo RV, Zarbock A, Götte M . 6 . The role for decorin in delayed-type hypersensitivity . Journal of Immunology . 187 . 11 . 6108–19 . December 2011 . 22043007 . 5070385 . 10.4049/jimmunol.1100373 .
9. Bocian C, Urbanowitz AK, Owens RT, Iozzo RV, Götte M, Seidler DG . Decorin potentiates interferon-γ activity in a model of allergic inflammation . The Journal of Biological Chemistry . 288 . 18 . 12699–711 . May 2013 . 23460644 . 3642316 . 10.1074/jbc.M112.419366 . free .
10. Schönherr E, Broszat M, Brandan E, Bruckner P, Kresse H . Decorin core protein fragment Leu155-Val260 interacts with TGF-beta but does not compete for decorin binding to type I collagen . Archives of Biochemistry and Biophysics . 355 . 2 . 241–8 . July 1998 . 9675033 . 10.1006/abbi.1998.0720 .
11. Santra M, Reed CC, Iozzo RV . Decorin binds to a narrow region of the epidermal growth factor (EGF) receptor, partially overlapping but distinct from the EGF-binding epitope . The Journal of Biological Chemistry . 277 . 38 . 35671–81 . September 2002 . 12105206 . 10.1074/jbc.M205317200 . 20575381 . free .
12. Iozzo RV, Moscatello DK, McQuillan DJ, Eichstetter I . Decorin is a biological ligand for the epidermal growth factor receptor . The Journal of Biological Chemistry . 274 . 8 . 4489–92 . February 1999 . 9988678 . 10.1074/jbc.274.8.4489 . 32175802 . free .
13. Hildebrand A, Romarís M, Rasmussen LM, Heinegård D, Twardzik DR, Border WA, Ruoslahti E . Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta . The Biochemical Journal . 302 (Pt 2) . 2 . 527–34 . September 1994 . 8093006 . 1137259 . 10.1042/bj3020527 .
14. Takeuchi Y, Kodama Y, Matsumoto T . Bone matrix decorin binds transforming growth factor-beta and enhances its bioactivity . The Journal of Biological Chemistry . 269 . 51 . 32634–8 . December 1994 . 10.1016/S0021-9258(18)31681-8 . 7798269 . free .
15. Merline R, Moreth K, Beckmann J, Nastase MV, Zeng-Brouwers J, Tralhão JG, Lemarchand P, Pfeilschifter J, Schaefer RM, Iozzo RV, Schaefer L . 6 . Signaling by the matrix proteoglycan decorin controls inflammation and cancer through PDCD4 and MicroRNA-21 . Science Signaling . 4 . 199 . ra75 . November 2011 . 22087031 . 5029092 . 10.1126/scisignal.2001868 .