DCN

Fig1. Decorin exhibits promiscuity in its ability to alter tumorigenesis via regulation of angiogenesis, autophagy, and inflammation. (Liliana Schaefer, 2017)

What is DCN protein?

DCN (decorin) gene is a protein coding gene which situated on the long arm of chromosome 12 at locus 12q21. The protein encoded by this gene is a small cellular or pericellular matrix proteoglycan that is closely related in structure to biglycan protein. The encoded protein 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. It contains one attached glycosaminoglycan chain. This protein is capable of suppressing the growth of various tumor cell lines. The DCN protein is consisted of 359 amino acids and its molecular mass is approximately 39.7 kDa.

What is the function of DCN protein?

DCN proteins can bind and inhibit the activity of a variety of growth factors and cytokines, thereby regulating cell growth and differentiation. It can also promote the proliferation and migration of fibroblasts, vascular endothelial cells and other cells, accelerate tissue repair and regeneration. Can eliminate free radicals, reduce oxidative damage. It can affect the function of immune cells such as T cells and B cells and regulate immune response.

DCN Related Signaling Pathway

Decorin proteins can bind and inhibit the activity of TGF-β receptors, thereby blocking the conduction of TGF-β signaling pathways. Decorin proteins can bind and activate the Wnt/β-catenin signaling pathway, thereby promoting cell proliferation and differentiation. Decorin protein can bind and inhibit the activity of BMP receptor, thus blocking the conduction of BMP signaling pathway. Decorin proteins can bind and activate ERK signaling pathways, thereby promoting cell proliferation and differentiation.

DCN Related Diseases

DCN is associated with a variety of organ diseases, including kidney, liver, cardiovascular diseases, such as liver fibrosis, cirrhosis, glomerulosclerosis, renal interstitial fibrosis, atherosclerosis, myocardial infarction, etc. Abnormal DCN is also associated with tumor development.

Bioapplications of DCN

DCN can promote cell proliferation, differentiation and migration, and accelerate tissue repair and regeneration. As a result, several treatments for tissue repair and regeneration have successfully harnessed the function of the DCN protein. It's also used for cartilage repair.

Case Study 1: Tze-Hong Wong, 2020

Aging impairs the IGF-I signaling of bone marrow mesenchymal stem cells (bmMSCs), but the mechanism is unclear. Here, the researchers found that the ability to auto-phosphorylate IGF-I receptor (IGF-IR) in response to IGF-I was decreased in the bmMSCs of aged donors. Conversely, data showed that decorin (DCN) expression was prominently increased in aged bmMSCs, and that under IGF-I treatment, DCN knockdown in serum-starved aged bmMSCs potentiated their mitogenic activity and IGF-IR auto-phosphorylation, whereas DCN overexpression in serum-starved adult bmMSCs decreased both activities. Co-immunoprecipitation assays suggested that IGF-I and DCN bound to IGF-IR in a competitive manner. Online MethPrimer predicted 4 CpG islands (CGIs) in the introns of DCN gene. RT-qPCR and bisulfite sequencing showed that dimethyloxalylglycine, an inhibitor of DNA demethylation, increased DCN mRNA expression and CGI-I methylation in adult bmMSCs, whereas 5-aza-2'-deoxycytidine, a DNA methylation inhibitor, decreased DCN mRNA expression and CGI-I methylation in aged bmMSCs, and ultimately enhanced the proliferation of serum-starved aged bmMSCs under IGF-I stimulation.

Fig1. Western blot analyses of DCN levels. Representative blots of the DCN levels in the Aged-1, Aged-2, Adult-1, and Adult-2 cells are shown.

Fig2. Effect of IGF-I on the binding of DCN to IGF-IR.

Case Study 2: Pinki Nandi, 2018

The origin and regulation of stem cells sustaining trophoblast renewal in the human placenta remain unclear. Decorin, a leucine-rich proteoglycan restrains trophoblast proliferation, migration/invasiveness and endovascular differentiation, and local decorin overproduction is associated with preeclampsia (PE). Here, the researchers tested the role of decorin in human trophoblast stem cell self-renewal and differentiation, using two models: an immortalized first trimester trophoblast cell line HTR-8/SVneo (HTR) and freshly isolated primary trophoblast (p-trophoblast) from early first trimester (6-9 weeks) placentas. Self-renewal capacity was measured by spheroid forming ability of single cells on ultra-low attachment plates for multiple generations. Markers of embryonic stem (ES) cells, trophoblast stem (TS) cells and trophoblast were used to identify stem cell hierarchy. Differentiation markers for syncytial and extravillous (EVT) pathways were employed to identify differentiated cells. Bewo cells were additionally used to explore DCN effects on syncytialization. Results reveal that the incidence of spheroid forming stem-like cells was 13-15% in HTR and 0.1-0.4%, in early first trimester p-trophoblast, including a stem cell hierarchy of two populations of ES and TS-like cells. DCN restrained ES cell self-renewal, promoted ES to TS transition and maintenance of TS cell stem-ness, but inhibited TS cell differentiation into both syncytial and EVT pathways.

Fig3. Shows DCN effects (250 nM, having no effect on cell viability), on spheroid numbers and spheroid forming efficiency during the first generation.

Fig4. Shows representative images of DCN effects on syncytialization markers (loss of junctional E-cadherin and stimulation of CGB expression) by immunostaining in p-trophoblast cells grown as monolayer.

DCN has several biochemical functions, for example, collagen binding,extracellular matrix binding,glycosaminoglycan binding. Some of the functions are cooperated with other proteins, some of the functions could acted by DCN itself. We selected most functions DCN had, and list some proteins which have the same functions with DCN. You can find most of the proteins on our site.

DCN has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with DCN here. Most of them are supplied by our site. Hope this information will be useful for your research of DCN.

INS;INS;IGF2;INSR;FGF2;Fgf7;Fgf8;Fgf1