Iefly by fibroblasts, stressed vascular endothelial cells, and SMCs. Its name is derived from the fact that it `decorates’ collagen, and it was initially characterized by its high-affinity interactions with collagen fibers [117] and its part inside the regulation of collagen fibrillogenesis [118-121]. Decorin was the earliest collagen regulatory SLRP to become recognized as a modulator of cell proliferation [122]. According to its structural and signal transduction functions, decorin is described as a bi-functional proteoglycan [123, 124], acting each as a signaling molecule as well as a structural ECM element [51, 125-127]. The LRR motifs are frequently regarded to become internet sites of protein rotein interactions; inside the decorin core protein these websites interact with quite a few receptor tyrosine kinases), like the epidermal development factor receptor (EGFR), the insulin-like growth element 1 receptor (IGF-1R), MET (proto-oncogene), plus the vascular endothelial growth element receptor 2 (VEGFR2), too because the low-density lipoprotein receptor-related protein 1 (LRP1) and innate immunity receptors (see [127, 128] for review), as discussed beneath. Early studies of decorin have been focused mostly on its anti-proliferative and anti-fibrogenic/ anti-scarring functions (reviewed in [127, 128]). Inside the 1990s, decorin was shown to interact with TGF [129, 130], and its anti-fibrotic functions were investigated inside a variety of biological systems [51, 131-137]. The last LRR motif of decorin also interacts with connective tissue development element and this interaction was shown to restrict production of fibronectin and collagen sort III, thus influencing turnover and production from the ECM [138]. The anti-proliferative and anti-tumorigenic functions were attributed to interactions from the core protein with and downregulation of EGFR, and elevated apoptosis [139]. Studies applying exogenous decorin and gene-targeted mice deficient in decorin further indicated the modulation by this proteoglycan of cyclin-dependent kinase inhibitor-1 (p21/CIP) signaling pathways and suppression of proliferation [140-142].Author Manuscript Author Manuscript Author Manuscript Author ManuscriptJ Intern Med. Author manuscript; offered in PMC 2016 November 01.Hultg dh-Nilsson et al.PageDecorin, as well as biglycan and lumican, has roles inside the innate immune response and inflammation. Circulating decorin levels increase throughout inflammation in patients with sepsis as well as inside a septic mouse model and, as shown in pull-down assays in cell culturebased expression systems, decorin interacts with each TLR2 and TLR4 [143]. The outcomes indicate that decorin promotes TLR2- and TLR4-mediated downstream induction in the proinflammatory cytokines tumor necrosis factor- and IL-12 at the protein level [143]. An intermediary in this pathway seems to be decorin-driven upregulation of the proinflammatory programmed cell death 4 (PDCD4) protein, that is a translational repressor of IL-10. In addition, the lowering of IL-10 was suggested to be M-CSF R Proteins Formulation resulting from a decorin-associated decrease in TGFand the IL-12 Proteins Recombinant Proteins resultant reduction inside the microRNA miR 21, which itself contributes to elevating IL-10. Added inflammation-related functions of decorin consist of its part in downregulating the expression levels of intercellular adhesion molecule (ICAM)-1 and syndecan-1 and inhibition of polymorphonuclear leukocyte adhesion to the endothelial layer of blood vessels [144]. Decorin has also been reported to drive autophagy in endothelial cells.
