Department of Physiology, Yonsei University College of Medicine, 50 Yonseiro, Seodaemun-gu, Seoul, 03722, Korea.
Pflugers Arch. 2024 Oct;476(10):1479-1492. doi: 10.1007/s00424-024-02983-4. Epub 2024 Jul 2.
Piezo1 mechanosensitive ion channel plays a important role in vascular physiology and disease. This study aimed to elucidate the altered signaling elicited by Piezo1 activation in the arteries of type 2 diabetes. Ten- to 12-week-old male C57BL/6 (control) and type 2 diabetic mice (db/db) were used. The second-order mesenteric arteries (~ 150 μm) were used for isometric tension experiments. Western blot analysis and immunofluorescence staining were performed to observe protein expression. Piezo1 was significantly decreased in mesenteric arteries of type 2 diabetic mice compared to control mice, as analyzed by western blot and immunofluorescence staining. Piezo1 agonist, Yoda1, concentration-dependently induced relaxation of mesenteric arteries in both groups. Interestingly, the relaxation response was significantly greater in control mice than in db/db mice. The removal of endothelium reduced relaxation responses induced by Yoda1, which was greater in control mice than db/db mice. Furthermore, the relaxation response was reduced by pre-treatment with various types of K channel blockers in endothelium-intact arteries in control mice. In endothelium-denuded arteries, pre-incubation with charybdotoxin, an Ca-activated K channel (BK channel) blocker, significantly attenuated Yoda1-induced relaxation in db/db mice, while there was no effect in control mice. Co-immunofluorescence staining showed co-localization of Piezo1 and BK channel was more pronounced in db/db mice than in control mice. These results indicate that the vascular responses induced by Piezo1 activation are different in the mesenteric resistance arteries in type 2 diabetic mice.
Piezo1 机械敏感性离子通道在血管生理学和疾病中发挥着重要作用。本研究旨在阐明 2 型糖尿病小鼠动脉中 Piezo1 激活引起的信号改变。使用 10-12 周龄雄性 C57BL/6（对照）和 2 型糖尿病小鼠（db/db）。使用二级肠系膜动脉（~150μm）进行等长张力实验。进行 Western blot 分析和免疫荧光染色以观察蛋白表达。Western blot 和免疫荧光染色分析表明，与对照组相比，2 型糖尿病小鼠的肠系膜动脉中 Piezo1 明显减少。Piezo1 激动剂 Yoda1 浓度依赖性地诱导两组肠系膜动脉舒张。有趣的是，对照组的舒张反应明显大于 db/db 组。去除内皮后，Yoda1 诱导的舒张反应减少，对照组大于 db/db 组。此外，在有完整内皮的动脉中，用各种类型的 K 通道阻滞剂预处理可减少对照组中 Yoda1 诱导的舒张反应。在内皮缺失的动脉中，预先孵育 charybdotoxin（一种 Ca 激活的 K 通道（BK 通道）阻滞剂）可显著减弱 db/db 小鼠中 Yoda1 诱导的舒张反应，而对对照组没有影响。共免疫荧光染色显示，Piezo1 和 BK 通道在 db/db 小鼠中的共定位比在对照组中更明显。这些结果表明，Piezo1 激活引起的血管反应在 2 型糖尿病小鼠的肠系膜阻力动脉中不同。
