Interactions of mechanotransduction pathways.
Integrins may serve as mechanosensors in endothelial cells (ECs): shear stress causes integrin-Shc association, assembly of the signaling complex and then leads to JNK activation. Flow also mediates selective and cell-specific alterations in vascular cell G-protein expression that correlate with changes in cell-signalling, G-protein functionality and modulate Ca2+ concentration. In this study, we explored the cross-talks between EC membrane mechanosensors, such as integrins, ion channels, and G-proteins in shear stress-induced signal transduction by their specific inhibition. Confluent monolayer of bovine aortic endothelial cells (BAECs) were incubated with or without specific inhibitors prior to shearing experiments. Our results showed an attenuation of integrin-Shc association under shear stress with RGD, and with PTX, but not with BAPTA/AM. The inhibitions of shear-activated JNK are similar for RGD and PTX. However, unlike for integrin association, the chelation of calcium reduced JNK activation. These results provide several lines of evidence of the interactions between different mechanosensors in ECs. First, integrin-Shc association required cell attachment and G-protein activity, but not intracellular calcium. Second, shear-induced JNK activation is regulated by multiple mechano-sensing mechanisms such as integrin, G-protein and calcium concentration.
Labrador
Vénus
V
Mechanobiology of Cells and Tissues, UMR CNRS 7563 Medicine Faculty, Vandoeuvre, France. labrador@hemato.u-nancy.fr
Chen
Kuang-Den
KD
Li
Yi-Shuan
YS
Muller
Sylvaine
S
Stoltz
Jean-François
JF
Chien
Shu
S
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D002118:Calcium / Q000502:physiology; D002417:Cattle; D018929:Cell Culture Techniques / Q000379:methods; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000502:physiology; D016023:Integrins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases; D008465:Mechanoreceptors / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins; D013314:Stress, Mechanical
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D016023:Integrins; D011506:Proteins; D055765:Shc Signaling Adaptor Proteins; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins; D002118:Calcium