ADAMTS-1 and syndecan-4 intersect in the regulation of cell migration and angiogenesis.
J Cell Sci
; 133(7)2020 04 08.
Article
en En
| MEDLINE
| ID: mdl-32269093
ABSTRACT
ADAMTS-1 is an extracellular protease with critical roles in organogenesis and angiogenesis. Here we demonstrate a functional convergence of ADAMTS-1 and the transmembrane heparan sulfate proteoglycan syndecan-4 in influencing adhesion, migration and angiogenesis. Knockdown of ADAMTS-1 in endothelial cells resulted in a parallel reduction in cell surface syndecan-4, attributable to increased matrix metalloproteinase-9 (MMP9) activity. Knockdown of either ADAMTS-1 or syndecan-4 increased cellular responses to vascular endothelial growth factor A isoform VEGFA164, and increased ex vivo aortic ring microvessel sprouting. On fibronectin, knockdown of either protein enhanced migration and promoted formation of long α5 integrin-containing fibrillar adhesions. However, integrin α5 null cells still showed increased migration in response to ADAMTS-1 and syndecan-4 siRNA treatment. Plating of naïve endothelial cells on cell-conditioned matrix from ADAMTS-1 and syndecan-4 knockdown cells demonstrated that the altered adhesive behaviour was matrix dependent, and this correlated with a lack of expression of fibulin-1 an extracellular matrix co-factor for ADAMTS-1 that is known to inhibit migration. These findings support the notion that ADAMTS-1 and syndecan-4 are functionally interconnected in regulating cell migration and angiogenesis, via collaboration with MMP9 and fibulin-1.This article has an associated First Person interview with the first author of the paper.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Factor A de Crecimiento Endotelial Vascular
/
Sindecano-4
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Cell Sci
Año:
2020
Tipo del documento:
Article