title: HPSE-1 expression and functionality in differentiating neural cells.
abstract: The study of cellular differentiation encompasses many vital parts of biology and medicine. Heparan sulfate proteoglycans (HSPG) are essential and ubiquitous macromolecules associated with the cell surface and extracellular matrix (ECM) of a wide range of cells and tissues. Heparan sulfate chains (HS) of HSPG bind and sequester a multitude of extracellular ligands, including growth factors, cytokines, chemokines, enzymes, and lipoproteins. Enzymatic degradation of HS is therefore involved in processes such as cell proliferation, migration, and differentiation. Heparanase (HPSE-1) is an HS degradative enzyme associated with inflammation and lipid metabolism and is a critical molecular determinant in cancer metastasis. The enzyme acts as an endo-beta-D-glucuronidase, which degrades HS at specific intrachain sites, resulting in HS fragments of discrete molecular weights that retain biological function. HPSE-1's relevance as the only example of cloned/purified mammalian HS degradative enzyme led us to investigate its functionality in human olfactory epithelium (HOE) cells as a paradigm for HPSE-1's roles in neural cell differentiation. We provide the first evidence of 1) HPSE-1 presence in HOE cells and 2) a highly significant increase of HPSE-1 mRNA and enzyme activity in differentiating vs. proliferating HOE cells. Our data suggest that an augmented HPSE-1 activity may represent a physiological mechanism involved in neural cellular differentiation.
authors.affiliation: Dipartimento di Patologia e Medicina Sperimentale e Clinica (DPMSC), and Centro Interdipartimentale di Medicina Rigenerativa (CIME), University of Udine, Udine, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Moretti
authors.forename: Neeta Devi
authors.initials: ND
authors.lastname: Sinnappah-Kang
authors.forename: Matteo
authors.initials: M
authors.lastname: Toller
authors.forename: Francesco
authors.initials: F
authors.lastname: Curcio
authors.forename: Dario
authors.initials: D
authors.lastname: Marchetti
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology; D005966:Glucuronidase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000378:metabolism*; D009831:Olfactory Mucosa / Q000166:cytology / Q000294:innervation; D018034:Olfactory Receptor Neurons / Q000502:physiology; D012313:RNA; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D012313:RNA; D012333:RNA, Messenger; D000099175:Heparanase; C034477:RNA primers