Role of ligand-specific integrins in endothelial cell alignment and elongation induced by cyclic strain.
Ligand-specific integrins are thought to play a critical role in regulating multiple biological processes. However, the mechanisms by which ligand-specific integrins mediate external stimuli and activate intracellular signaling pathways remain to be elucidated. The aim of this study was to clarify the role of ligand-specific integrins in the morphological changes induced by cyclic strain (CS) via the p38 mitogen-activated protein kinase (p38 MAPK) pathway. Endothelial cells (ECs) were cultured on collagen (a ligand for integrin alpha 2 beta1, but not for alpha 5 and beta 4)-coated flexible plates and incubated for 24 h with or without anti-alpha2 integrin antibody (anti-alpha2), anti-alpha5, anti-beta1, or anti-beta4. ECs were then subjected to 15.6% average CS at 60 cycles/min up to 24 h. After exposure to CS, the cell shape index (defined as (4pi x cell area)/(cell perimeter)(2)), the cell orientation angle, and activation of p38 MAPK were assessed. ECs in the absence of integrin-blocking antibodies were elongated and aligned in response to CS. Anti-alpha 2 and anti-beta1 abolished both morphological changes of ECs as well as the activation of p38 MAPK. In contrast, anti-alpha 5 and anti-beta 4 inhibited neither morphological changes of ECs nor the activation of p38 MAPK. Our results indicate that ligand-specific integrins play a crucial role in the morphological changes of ECs induced by CS via the p38 MAPK pathway.
Hirayama
Yo
Y
Department of Surgery, Section of Vascular Surgery, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Sumpio
Bauer E
BE
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D002417:Cattle; D016764:Cell Polarity / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D039421:Integrin alpha2 / Q000378:metabolism; D039482:Integrin alpha5 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D039663:Integrin beta4 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D008024:Ligands; D008954:Models, Biological; D010766:Phosphorylation / Q000187:drug effects; D013314:Stress, Mechanical; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D019138:Antibodies, Blocking; D039421:Integrin alpha2; D039482:Integrin alpha5; D019012:Integrin beta1; D039663:Integrin beta4; D016023:Integrins; D008024:Ligands; D048051:p38 Mitogen-Activated Protein Kinases