Vascular endothelial growth factor and substrate mechanics regulate in vitro tubulogenesis of endothelial progenitor cells

Autor: Donny Hanjaya-Putra, Doug Ceci, Jane Yee, Sharon Gerecht, Rachel Truitt, Derek Yee
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Male
Endothelium
Angiogenesis
extracellular matrix
02 engineering and technology
CDC42
Matrix metalloproteinase
Biology
Extracellular matrix
03 medical and health sciences
chemistry.chemical_compound
angiogenesis
Microscopy
Electron
Transmission
Cell Movement
medicine
Humans
Progenitor cell
Cells
Cultured
030304 developmental biology
endothelial progenitor cells
0303 health sciences
vascular endothelial growth factor
Vascular Endothelial Growth Factors
Stem Cells
Infant
Newborn
Endothelial Cells
Cell Differentiation
Hydrogels
Cell Biology
Mechanics
Articles
021001 nanoscience & nanotechnology
tubulogenesis
Matrix Metalloproteinases
Cell biology
Vascular endothelial growth factor
medicine.anatomical_structure
chemistry
Tube morphogenesis
cardiovascular system
Molecular Medicine
Female
Endothelium
Vascular
0210 nano-technology
Cell Division
Zdroj: Journal of Cellular and Molecular Medicine
ISSN: 1582-4934
1582-1838
Popis: Endothelial progenitor cells (EPCs) in the circulatory system have been suggested to maintain vascular homeostasis and contribute to adult vascular regeneration and repair. These processes require that EPCs break down the extracellular matrix (ECM), migrate, differentiate and undergo tube morphogenesis. Evidently, the ECM plays a critical role by providing biochemical and biophysical cues that regulate cellular behaviour. Using a chemically and mechanically tunable hydrogel to study tube morphogenesis in vitro, we show that vascular endothelial growth factor (VEGF) and substrate mechanics co-regulate tubulogenesis of EPCs. High levels of VEGF are required to initiate tube morphogenesis and activate matrix metalloproteinases (MMPs), which enable EPC migration. Under these conditions, the elasticity of the substrate affects the progression of tube morphogenesis. With decreases in substrate stiffness, we observe decreased MMP expression while increased cellular elongation, with intracellular vacuole extension and coalescence to open lumen compartments. RNAi studies demonstrate that membrane type 1-MMP (MT1-MMP) is required to enable the movement of EPCs on the matrix and that EPCs sense matrix stiffness through signalling cascades leading to the activation of the RhoGTPase Cdc42. Collectively, these results suggest that coupled responses for VEGF stimulation and modulation of substrate stiffness are required to regulate tube morphogenesis of EPCs.
Databáze: OpenAIRE
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