title: Recent data concerning heparanase: focus on fibrosis, inflammation and cancer.
abstract: Heparanase (HPSE) is a multitasking protein characterized by enzymatic and non-enzymatic activities. By means of its enzymatic activity, HPSE catalyzes the cutting of the side chains of heparan sulfate (HS) proteoglycans, thereby inducing the remodeling of the extracellular matrix and basement membranes. Thanks to the cleavage of HS, HPSE also promotes the release and diffusion of several HS-linked molecules such as growth factors, cytokines and enzymes. In addition to degrading HS chains, HPSE has non-enzymatic functions that trigger several signaling pathways. This signaling activity is achieved by interacting with transmembrane proteins, activating kinases such as Akt and Src, or modulating the activity of factors such as FGF-2 and TGF-β. Several studies have recently highlighted a possible intracellular activity for HPSE, particularly at nuclear level. While HPSE activity is quite limited in physiological conditions, its demonstrated increasing involvement in various pathological conditions, such as in tumor progression and renal disease, have attracted the attention of a growing number of researchers. The fact that no other molecule is capable of performing the same function as HPSE makes this enzyme an attractive potential target of medical treatment. With this short conceptual overview, we aim to provide an update on current knowledge concerning the HPSE protein in the experimental and clinical settings, paying particular attention to its role in fibrosis, inflammation and cancer.
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Secchi
authors.forename: Valentina
authors.initials: V
authors.lastname: Masola
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Zaza
authors.forename: Antonio
authors.initials: A
authors.lastname: Lupo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Gambaro
authors.forename: Maurizio
authors.initials: M
authors.lastname: Onisto
mesh_terms: D058750:Epithelial-Mesenchymal Transition; D005355:Fibrosis / Q000201:enzymology; D005966:Glucuronidase / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000201:enzymology*; D007668:Kidney / Q000201:enzymology / Q000473:pathology; D008954:Models, Biological; D009369:Neoplasms / Q000201:enzymology*; D015398:Signal Transduction; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D006497:Heparan Sulfate; D000099175:Heparanase