Syndecans in Inflammation at a Glance

Abstract

Syndecans are transmembrane proteoglycans with heparan and chondroitin sulfate chains attached to their extracellular domain. Like many proteoglycans, they interact with a large number of ligands, such as growth factors, adhesion receptors, soluble small molecules, proteinases, and other extracellular matrix proteins to initiate downstream signaling pathways. Syndecans play a major role in inflammation, mainly by regulating leukocyte extravasation and cytokine function. At the same time, syndecans can undergo cytokine mediated changes in their expression levels during inflammation. The function of syndecans during inflammation appears to depend on the stage of inflammation, sulfation of heparan/chondroitin sulfate chains, the rate of ectodomain shedding and the solubility of the ectodomains. From the current literature, it is clear that syndecans are not only involved in the initial recruitment of pro-inflammatory molecules but also in establishing a balanced progression of inflammation. This review will summarize how cell surface and soluble syndecans regulate multiple aspects of inflammation.

Heparan Sulfate Proteoglycan Signaling in Tumor Microenvironment

“…In addition, HSPGs are involved in endocytosis and vesicular trafficking [18]. By acting as intermediaries between ECM and intracellular signaling pathways, HSPGs regulate a variety of physiological and pathological processes including tissue development, morphogenesis, cell proliferation, apoptosis, adhesion, motility, wound healing, inflammation, and tumorigenesis [10,11,17,[19][20][21][22][23][24][25][26][27][28].…”

Interplay between Cell-Surface Receptors and Extracellular Matrix in Skin

“…In line with this, syndecan-1 and syndecan-4 double knockout mice show increased P-cadherin levels in the epidermal stratum spinosum and stratum basale, and a disturbed organization of lower epidermal layers, while the suprabasal cells keep their cytoplasmic extensions reaching to the basement membrane [198]. Mechanistically, syndecans interact with transient receptor potential canonical (TRPC) calcium channels and may therefore be involved in regulating actin cytoskeleton, adhesion, junction assembly and cell migration via calcium homeostasis [198,199]. The interaction with TRPCs could also be important in the context of fibrosis.…”

“…Syndecans have been reported to have both pro-and anti-inflammatory effects, most likely depending on the underlying model, the tissue of focus or the stage of inflammation, as well as characteristics of their ectodomains [199]. In the skin disease psoriasiform dermatitis, syndecan-1 has been alluded to an anti-inflammatory function, since it regulates the homeostasis of an interleukin-17-producing subset of γδ-T-cells (Tγδ17) [200].…”

Heparan Sulfate Proteoglycans Biosynthesis and Post Synthesis Mechanisms Combine Few Enzymes and Few Core Proteins to Generate Extensive Structural and Functional Diversity

“…Cell-surface HSPGs and their shed ectodomains exhibit distinct biological activities. Shedding of HSPGs does notably take place during inflammation [ 215 ]. There, soluble ectodomains play major regulatory functions, by binding to inflammatory chemokines and thus affecting their bioavailability and organization of chemotactic gradients.…”