Open AccessBiology of the Heparanase–Heparan Sulfate Axis and Its Role in Disease Pathogenesis
Author(s) -
Israël Vlodavsky,
Uri Barash,
Hien M. Nguyen,
Shiming Yang,
Neta Ilan
Publication year - 2021
Publication title -
seminars in thrombosis and hemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 99
eISSN - 1098-9064
pISSN - 0094-6176
DOI - 10.1055/s-0041-1725066
Subject(s) - heparanase , heparan sulfate , microbiology and biotechnology , syndecan 1 , glycocalyx , extracellular matrix , perlecan , biology , cell adhesion , signal transduction , cell , proteoglycan , biochemistry
Cell surface proteoglycans are important constituents of the glycocalyx and participate in cell-cell and cell-extracellular matrix (ECM) interactions, enzyme activation and inhibition, and multiple signaling routes, thereby regulating cell proliferation, survival, adhesion, migration, and differentiation. Heparanase, the sole mammalian heparan sulfate degrading endoglycosidase, acts as an "activator" of HS proteoglycans, thus regulating tissue hemostasis. Heparanase is a multifaceted enzyme that together with heparan sulfate, primarily syndecan-1, drives signal transduction, immune cell activation, exosome formation, autophagy, and gene transcription via enzymatic and nonenzymatic activities. An important feature is the ability of heparanase to stimulate syndecan-1 shedding, thereby impacting cell behavior both locally and distally from its cell of origin. Heparanase releases a myriad of HS-bound growth factors, cytokines, and chemokines that are sequestered by heparan sulfate in the glycocalyx and ECM. Collectively, the heparan sulfate-heparanase axis plays pivotal roles in creating a permissive environment for cell proliferation, differentiation, and function, often resulting in the pathogenesis of diseases such as cancer, inflammation, endotheliitis, kidney dysfunction, tissue fibrosis, and viral infection.