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Related Experiment Videos

Interactions of mechanotransduction pathways.

Vénus Labrador1, Kuang-Den Chen, Yi-Shuan Li

  • 1Mechanobiology of Cells and Tissues, UMR CNRS 7563 Medicine Faculty, Vandoeuvre, France. labrador@hemato.u-nancy.fr

Biorheology
|November 28, 2002
PubMed
Summary

Endothelial cells use integrins, G-proteins, and calcium channels as mechanosensors. Shear stress activates JNK signaling through these pathways, revealing complex cross-talk between cellular sensors.

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Area of Science:

  • Cell Biology
  • Biophysics
  • Mechanobiology

Background:

  • Endothelial cells (ECs) sense mechanical forces like shear stress.
  • Integrins and G-proteins are implicated in EC mechanotransduction.
  • Shear stress influences G-protein expression, signaling, and intracellular calcium concentration.

Purpose of the Study:

  • To investigate the interplay between EC membrane mechanosensors (integrins, ion channels, G-proteins) in shear stress-induced signal transduction.
  • To elucidate the specific roles of integrins, G-proteins, and calcium in shear-activated JNK signaling.

Main Methods:

  • Utilized confluent monolayers of bovine aortic endothelial cells (BAECs).
  • Applied specific inhibitors (RGD, PTX, BAPTA/AM) targeting mechanosensors.

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  • Performed shearing experiments to analyze protein-protein interactions and signaling pathway activation (JNK).

    • Main Results:

    • Shear stress-induced integrin-Shc association was attenuated by RGD and PTX, but not BAPTA/AM.
    • Inhibition of shear-activated JNK was similar with RGD and PTX.
    • Calcium chelation (BAPTA/AM) reduced JNK activation, unlike its effect on integrin association.

    Conclusions:

    • Integrin-Shc association under shear stress depends on cell attachment and G-protein activity, but not intracellular calcium.
    • Shear-induced JNK activation is regulated by multiple mechanosensing pathways involving integrins, G-proteins, and calcium concentration.
    • Demonstrated cross-talk between distinct mechanosensors in endothelial cells.