DCN

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.

Fig1. Schema of proposed DCN action on stem cell hierarchy. (Pinki Nandi, 2018)

Fig2. Decorin interacts with multiple growth factor signaling pathways crucial for cancer growth. (Tero A H Järvinen, 2015)

DCN involved in several pathways and played different roles in them. We selected most pathways DCN participated on our site, such as A tetrasaccharide linker sequence is required for GAG synthesis, CS/DS degradation, Chondroitin sulfate biosynthesis, which may be useful for your reference. Also, other proteins which involved in the same pathway with DCN were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

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