Jiangsu Key Laboratory for Functional Substance of Chinese Medicine, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Jiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Nano Lett. 2023 Feb 22;23(4):1555-1563. doi: 10.1021/acs.nanolett.2c05099. Epub 2023 Feb 2.
Kidney stones, represented by the calcium oxalate (CaOx) type, are highly prevalent and recrudescent. Cumulative evidence shows regular consumption of lemonade intervenes with stone development. However, the detailed mechanism remains obscure. Here, extracellular vesicle-like nanoparticles (LEVNs) isolated from lemonade are demonstrated to traffick from the gut to the kidney, primarily enriched in tubule cells. Oral administration of LEVNs significantly alleviates the progression of kidney stones in rats. Mechanistically, in addition to altering the crystallization of CaOx toward a less stable subtype, LEVNs suppress the CaOx-induced endoplasmic reticulum stress response of tubule cells, as indicated by homeostasis of specific signaling molecules and restoration of subcellular function, thus indirectly inhibiting stone formation. To exercise this regulation, endocytosed LEVNs traffick along the microtubules throughout the cytoplasm and are eventually recruited into lysosomes. In conclusion, this study reveals a LEVNs-mediated mechanism against renal calculi and provides positive evidence for consumption of lemonade preventing stone formation.
肾结石以草酸钙（CaOx）类型为代表，具有高发性和复发性。累积证据表明，经常饮用柠檬水可干预结石的形成。然而，其详细机制尚不清楚。本研究中，从柠檬汁中分离出的细胞外囊泡样纳米颗粒（LEVNs）被证明可以从肠道转运到肾脏，主要富集在肾小管细胞中。口服 LEVNs 可显著减轻大鼠肾结石的进展。在机制上，除了改变 CaOx 的结晶向更不稳定的亚型外，LEVNs 还抑制了 CaOx 诱导的肾小管细胞内质网应激反应，这表现为特定信号分子的稳态和亚细胞功能的恢复，从而间接抑制结石形成。为了发挥这种调节作用，内吞的 LEVNs 沿着整个细胞质中的微管运输，并最终被招募到溶酶体中。总之，这项研究揭示了一种 LEVNs 介导的抗肾结石机制，并为饮用柠檬水预防结石形成提供了积极的证据。
