Low-intensity pulsed ultrasound in combination with SonoVue induces cytotoxicity of human renal glomerular endothelial cells via repression of the ERK1/2 signaling pathway

Objectives: Low-intensity pulsed ultrasound (LIPUS) and SonoVue have been used widely for diagnosis and therapeutic treatment. The effects of LIPUS and SonoVue on the microvascular system and underlying molecular mechanisms have not been established. Methods: Cultured human renal glomerular endothelial cells (HRGECs) were treated with 5-min ultrasonic irradiation, 20% SonoVue or the combination of both treatments. Cell proliferation, viablity, and apoptosis were measured by MTT assay, Trypan blue exclusion assay and flow cytometry, respectively. Activation of extracellular regulated protein kinases (ERK) were examined by Western blot. Results: We found that LIPUS and SonoVue alone do not induce cytotoxicity of HRGECs; however, the combination of the two treatments reduces cell proliferation and increases cell death. In addition, the combination of LIPUS and SonoVue suppressed the activation of ERK 1/2 in HRGRCs. With pretreatment of the inhibitor of ERK1/2 signaling, PD98059, LIPUS, and SonoVue does not induce additional cell death and inhibition of proliferation. Conclusions: LIPUS combined with SonoVue induces cytotoxicity of HRGECs via repression of the ERK1/2 signaling pathway.