Biology of the Heparanase-Heparan Sulfate Axis and Its Role in Disease Pathogenesis.
Journal
Seminars in thrombosis and hemostasis
ISSN: 1098-9064
Titre abrégé: Semin Thromb Hemost
Pays: United States
ID NLM: 0431155
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
entrez:
1
4
2021
pubmed:
2
4
2021
medline:
29
10
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33794549
doi: 10.1055/s-0041-1725066
pmc: PMC9097616
mid: NIHMS1801651
doi:
Substances chimiques
Heparitin Sulfate
9050-30-0
heparanase
EC 3.2.1.-
Glucuronidase
EC 3.2.1.31
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
240-253Subventions
Organisme : NCI NIH HHS
ID : R01 CA211752
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM098285
Pays : United States
Informations de copyright
Thieme. All rights reserved.
Déclaration de conflit d'intérêts
None declared.
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