Browsing by Subject "Heparan sulfate"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    Open Access
    HGSNAT enzyme deficiency results in accumulation of heparan sulfate in podocytes and basement membranes
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2019) Nagel, Lauren; Oliveira, Regiana; Pshezhetsky, Alexey V.; Morales, Carlos R.
    ucopolysaccharidosis III type C is a lysosomal storage disorder caused by the accumulation of heparan sulfate in lysosomes. The disorder occurs due to Heparan Acetyl-CoA: α-glucosaminide N- acetyltransferase (HGSNAT) deficiency, an enzyme which typically catalyzes the transmembrane acetylation of heparan sulfate, a basement membrane component. When the gene encoding this enzyme is mutated, it cannot perform the processing of heparan sulfate, leading to un-acetylated heparan sulfate build-up in the lysosomes of cells, causing a storage disorder. This defect has been studied primarily in brain and liver cells, but its effect on the structural integrity of the glomerulus is poorly known. The present study focuses on the effect of Hgsnat gene inactivation and heparan sulfate toxicity on the integrity of the renal corpuscle. This cortical structure was chosen because of its abundance of basement membranes and heparan sulfate as well as the renal corpuscle’s physiological importance in glomerular filtration. Light microscopy, electron microscopy, and immunocytochemistry of genetically modified mice revealed a buildup of lysosomes in the podocytes, suggesting that these cells are responsible for the processing of glomerular basement membranes
  • Thumbnail Image
    Publication
    Open Access
    Tumor promotion or suppression: Revisiting the role of EXT1 and heparan sulfate
    (2026) Hiroyuki Tomita; Akira Hara; Ayumi Niwa; Biología Celular e Histología; Universidad de Murcia, Departamento de Biología Celular e Histología
    Heparan sulfate (HS), a linear sulfated polysaccharide attached to proteoglycans, modulates the availability and activity of growth factors and cytokines to regulate cell signaling, adhesion, and migration. Exostosin-1 (EXT1), a key glycosyl-transferase for HS chain elongation, is increasingly implicated in cancer development and progression. Although originally identified as a tumor suppressor in hereditary multiple exostoses, EXT1 exhibits a complex, context-dependent role in cancer. The effects of EXT1 in cancer differ by cell and tumor type, exerting both tumor-suppressing and tumor-promoting effects. Notably, EXT1 also alters the tumor microenvironment via its expression in stromal fibroblasts and endothelial cells, further influencing tumor behavior. This review discusses the functions of HS and EXT1, emphasizing the roles of EXT1 in cancer and its microenvironment. A deeper understanding of these mechanisms may offer novel therapies targeting the HS biosynthetic pathway.