Biology of the Heparanase–Heparan Sulfate Axis and Its Role in Disease Pathogenesis
| Autor: | Neta Ilan, Hien M. Nguyen, Uri Barash, Shi-Ming Yang, Israel Vlodavsky |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cell Biology Exosome Article Glycocalyx 03 medical and health sciences Enzyme activator chemistry.chemical_compound 0302 clinical medicine medicine Humans Disease Heparanase Glucuronidase Cell growth Hematology Heparan sulfate Cell biology 030104 developmental biology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis Heparitin Sulfate Signal transduction Cardiology and Cardiovascular Medicine |
| Zdroj: | Semin Thromb Hemost |
| ISSN: | 1098-9064 0094-6176 |
| DOI: | 10.1055/s-0041-1725066 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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