FIGURE 4.

Mechanosensitive pathways involved in signaling triggered by stretching and/or shear stress. Ca²⁺ influx through Piezo1 and TRPV4 upregulates MT1-MMP, PI3K, JNK, promoting cell growth and proliferation, and HIFα, upregulating VEGF expression. PI3K is also upregulated by PECAM-1, integrin, and VE-Cadherin, which are activated by mechanical stress, and in turn, activate Akt. Akt’s downstream pathways activate NF-κB and mTOR, which facilitate cell growth and proliferation, as well as eNOS and NO, which enhance cell survival. Activated integrin, to which a macromolecular complex of FAK, Shc, Src, and Paxillin is bound, interacts with TIE-1/2. Rho and ROCK are activated by FAK and/or Src, upregulating in HIFα. Shc upregulates Grb2, SOS, and FRK 1/2, promoting cell proliferation and growth. Under shear stress and stretch YAP is translocated to the nucleus.