DCN

Official Full Name

decorin

Organism

Homo sapiens

GeneID

1634

Background

This gene encodes a member of the small leucine-rich proteoglycan family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the mature protein. This protein plays a role in collagen fibril assembly. Binding of this protein to multiple cell surface receptors mediates its role in tumor suppression, including a stimulatory effect on autophagy and inflammation and an inhibitory effect on angiogenesis and tumorigenesis. This gene and the related gene biglycan are thought to be the result of a gene duplication. Mutations in this gene are associated with congenital stromal corneal dystrophy in human patients. [provided by RefSeq, Nov 2015]

Synonyms

CSCD; PG40; PGII; PGS2; DSPG2; SLRR1B;

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Detailed Information

Decorin (DCN) is a small leucine-rich proteoglycan that is widely expressed in various tissues and cell types, including fibroblasts, chondrocytes, and synovial cells. The protein is primarily known for its role in regulating the extracellular matrix (ECM) and influencing cellular processes such as migration, proliferation, and differentiation. The DCN gene encodes for the production of decorin, and mutations in this gene have been associated with various diseases and conditions, including joint diseases, fibrosis, and cancer.

Structure And Function of Decorin

Decorin is a member of the small leucine-rich proteoglycan (SLRPG) family, which includes several other proteins such as biglycan, fibronectin, and collagen. The primary structure of decorin consists of a core protein and two glycosaminoglycan (GAG) chains, which are composed of disaccharide units of N-acetylgalactosamine and glucuronic acid (5). The core protein contains a conserved amino-terminal region, a collagen-binding domain, and a carboxy-terminal region with a high degree of variability.

The function of decorin is complex and depends on its interaction with various cell surface receptors and ECM components. Decorin has been shown to bind to type I, II, and III collagens, as well as fibronectin, and regulate the assembly and organization of the ECM. Additionally, decorin interacts with cell surface receptors such as integrins and discoidin domain receptors (DDRs), which mediate signaling pathways that regulate cell behavior.

Figure 1. The biological signaling network of decorin.

Role of DCN Gene in Disease Pathogenesis

Mutations in the DCN gene have been identified as a cause of various diseases and conditions. These mutations lead to alterations in the structure or function of decorin, which can result in pathological changes in the affected tissues. For example, mutations in the DCN gene have been associated with diseases such as fibrodysplasia ossificans progressiva (FOP), a genetic disorder characterized by the progressive replacement of muscle and soft tissues with bone. In FOP patients, DCN mutations lead to the production of a dysfunctional decorin protein that fails to bind to collagen and fibronectin, resulting in aberrant signaling and the activation of osteogenic cells.

Mutations in the DCN gene have also been implicated in various joint diseases, including osteoarthritis and rheumatoid arthritis. Decorin has been shown to regulate the synthesis and degradation of cartilage matrix components, and its deficiency leads to matrix instability and the progression of joint disease. Furthermore, decorin has been identified as a potential therapeutic target for fibrosis, as it has been shown to regulate the activity of myofibroblasts and the synthesis of ECM components in fibrotic tissues.

Therapies Targeting the DCN Gene or Its Protein Product

Given the important role of decorin in regulating ECM organization and cell behavior, targeting the DCN gene or its protein product has the potential to provide therapeutic benefits in various diseases. For example, strategies to increase decorin expression or to promote the production of functional decorin protein could be beneficial in diseases characterized by ECM abnormalities, such as fibrosis and joint diseases. In fact, several studies have demonstrated the potential of decorin-based therapies in preclinical models of fibrosis and arthritis.

References:

Dong, Yuanji et al. "The Role of Decorin in Autoimmune and Inflammatory Diseases." Journal of immunology research vol. 2022 1283383. 17 Aug. 2022, doi:10.1155/2022/1283383
Baghy, Kornélia et al. "Decorin in the Tumor Microenvironment." Advances in experimental medicine and biology vol. 1272 (2020): 17-38. doi:10.1007/978-3-030-48457-6_2

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