Basement Membrane Collagen Glycation Prevents Endothelial Cell Response to Strain due to Altered Focal Adhesion Formation

2011 ◽  
Author(s):  
Dannielle Solomon Figueroa ◽  
Alisa Morss Clyne
Keyword(s):  
Basement Membrane ◽  
Adhesion Formation ◽  
Blood Glucose Control ◽  
Protein Glycation ◽  
Cell Matrix ◽  
Basement Membrane Protein ◽  
Focal Adhesion Formation ◽  
Basement Membrane Collagen ◽  
Endothelial Cell Response ◽  
Collagen Glycation

Vascular morbidity and mortality are primary complications of diabetes and have been correlated with unregulated blood glucose control. Endothelial cells that line the vasculature are known to be dysfunctional in hyperglycemia (1). Furthermore, the high glucose environment promotes basement membrane protein glycation and enhanced cross-linking. This can increase matrix stiffness, decrease matrix degradation, and potentially alter the spatial distribution of cell-matrix binding sites.

A Cell Stretching System to Measure Endothelial Cell Cyclic Strain Response on Spatially Defined Basement Membrane

2009 ◽  
Author(s):  
Dannielle S. Figueroa ◽  
Alisa Morss Clyne
Keyword(s):  
Endothelial Cell ◽  
Basement Membrane ◽  
Cyclic Strain ◽  
Protein Glycation ◽  
Cross Linking ◽  
Strain Response ◽  
Basement Membrane Protein ◽  
Increased Risk ◽  
A Cell ◽  
Endothelial Cell Response

A principal concern in diabetes is the increased risk of vascular disease associated with unregulated blood glucose. Endothelial cells that line the vasculature are dysfunctional in hyperglycemia. The high glucose environment promotes basement membrane protein glycation and enhanced cross-linking, which can increase stiffness and may alter endothelial cell response to strain.

scholarly journals Vascular Endothelial-Cadherin Regulates Cytoskeletal Tension, Cell Spreading, and Focal Adhesions by Stimulating RhoA

2004 ◽  
Vol 15 (6) ◽  
pp. 2943-2953 ◽  
Author(s):  
Celeste M. Nelson ◽  
Dana M. Pirone ◽  
John L. Tan ◽  
Christopher S. Chen
Keyword(s):  
Adhesion Formation ◽  
Focal Adhesions ◽  
Cell Spreading ◽  
Cell Contact ◽  
Matrix Adhesion ◽  
Cell Matrix ◽  
Focal Adhesion Formation ◽  
Cytoskeletal Tension ◽  
Cell Matrix Adhesion ◽  
Cell Cell

Changes in vascular endothelial (VE)-cadherin–mediated cell-cell adhesion and integrin-mediated cell-matrix adhesion coordinate to affect the physical and mechanical rearrangements of the endothelium, although the mechanisms for such cross talk remain undefined. Herein, we describe the regulation of focal adhesion formation and cytoskeletal tension by intercellular VE-cadherin engagement, and the molecular mechanism by which this occurs. Increasing the density of endothelial cells to increase cell-cell contact decreased focal adhesions by decreasing cell spreading. This contact inhibition of cell spreading was blocked by disrupting VE-cadherin engagement with an adenovirus encoding dominant negative VE-cadherin. When changes in cell spreading were prevented by culturing cells on a micropatterned substrate, VE-cadherin–mediated cell-cell contact paradoxically increased focal adhesion formation. We show that VE-cadherin engagement mediates each of these effects by inducing both a transient and sustained activation of RhoA. Both the increase and decrease in cell-matrix adhesion were blocked by disrupting intracellular tension and signaling through the Rho-ROCK pathway. In all, these findings demonstrate that VE-cadherin signals through RhoA and the actin cytoskeleton to cross talk with cell-matrix adhesion and thereby define a novel pathway by which cell-cell contact alters the global mechanical and functional state of cells.

scholarly journals Hemidesmosomes modulate force generation via focal adhesions

2020 ◽  
Vol 219 (2) ◽  
Author(s):  
Wei Wang ◽  
Alba Zuidema ◽  
Lisa te Molder ◽  
Leila Nahidiazar ◽  
Liesbeth Hoekman ◽  
...  
Keyword(s):  
Adhesion Formation ◽  
Focal Adhesions ◽  
Traction Force ◽  
Force Generation ◽  
Mechanical Coupling ◽  
Cell Matrix ◽  
Focal Adhesion Formation ◽  
Integrin Α6β4 ◽  
Cell Matrix Adhesion ◽  
Laminin 332

Hemidesmosomes are specialized cell-matrix adhesion structures that are associated with the keratin cytoskeleton. Although the adhesion function of hemidesmosomes has been extensively studied, their role in mechanosignaling and transduction remains largely unexplored. Here, we show that keratinocytes lacking hemidesmosomal integrin α6β4 exhibit increased focal adhesion formation, cell spreading, and traction-force generation. Moreover, disruption of the interaction between α6β4 and intermediate filaments or laminin-332 results in similar phenotypical changes. We further demonstrate that integrin α6β4 regulates the activity of the mechanosensitive transcriptional regulator YAP through inhibition of Rho–ROCK–MLC– and FAK–PI3K–dependent signaling pathways. Additionally, increased tension caused by impaired hemidesmosome assembly leads to a redistribution of integrin αVβ5 from clathrin lattices to focal adhesions. Our results reveal a novel role for hemidesmosomes as regulators of cellular mechanical forces and establish the existence of a mechanical coupling between adhesion complexes.

scholarly journals Biosynthesis of basement membrane collagen by rabbit corneal endothelium in vitro.

1976 ◽  
Vol 251 (3) ◽  
pp. 730-733 ◽  
Author(s):  
N A Kefalides ◽  
J D Cameron ◽  
E A Tomichek ◽  
M Yanoff
Keyword(s):  
Basement Membrane ◽  
Corneal Endothelium ◽  
Basement Membrane Collagen ◽  
Membrane Collagen
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