Zamfirov Laura, Nguyen Ngoc-Minh, Fernández-Sánchez Maria Elena, Cambronera Ghiglione Paula, Teston Eliott, Dizeux Alexandre, Tiennot Thomas, Farge Emmanuel, Demené Charlie, Tanter Mickael
Institute Physics for Medicine Paris, ESPCI PSL Paris, INSERM U1273, CNRS UMR 8361, Paris Sciences et Lettres University, Paris, France.
Mechanics and Genetics of Embryonic and Tumoral Development team, Physics of Cells and Cancer UMR168, INSERM, Université PSL, Sorbonne Université, Institut Curie, Paris, France.
Nat Biomed Eng. 2025 May;9(5):742-753. doi: 10.1038/s41551-024-01300-9. Epub 2024 Dec 20.
Ultrasound generates both compressive and shear mechanical forces in soft tissues. However, the specific mechanisms by which these forces activate cellular processes remain unclear. Here we show that low-intensity focused ultrasound can activate the mechanosensitive RET signalling pathway. Specifically, in mouse colon tissues ex vivo and in vivo, focused ultrasound induced RET phosphorylation in colonic crypts cells, which correlated with markers of proliferation and stemness when using hours-long insonication. The activation of the RET pathway is non-thermal, is linearly related to acoustic pressure and is independent of radiation-force-induced shear strain in tissue. Our findings suggest that ultrasound could be used to regulate cell proliferation, particularly in the context of regenerative medicine, and highlight the importance of adhering to current ultrasound-safety regulations for medical imaging.
超声波在软组织中会产生压缩力和剪切力。然而，这些力激活细胞过程的具体机制仍不清楚。在这里，我们表明低强度聚焦超声可以激活机械敏感的RET信号通路。具体而言，在离体和体内的小鼠结肠组织中，聚焦超声诱导结肠隐窝细胞中的RET磷酸化，当进行长达数小时的超声照射时，这与增殖和干性标志物相关。RET通路的激活是非热的，与声压呈线性相关，并且与组织中辐射力诱导的剪切应变无关。我们的研究结果表明，超声可用于调节细胞增殖，特别是在再生医学背景下，并强调了遵守当前医学成像超声安全法规的重要性。
