高选择性人工 K+ 转运体逆转体内肝纤维化

JACS Au Pub Date : 2024-08-26 DOI:10.1021/jacsau.4c00521
Qiuping Zhang, Qinghong Liang, Guijiang Wang, Xiaopan Xie, Yin Cao, Nan Sheng, Zhiping Zeng, Changliang Ren
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引用次数: 0

摘要

肝纤维化是一种危及生命的疾病,目前缺乏临床有效的治疗药物。鉴于细胞内 K+ 平衡失调与肝纤维化的进展密切相关,开发人工 K+ 转运体,模仿其天然对应物在调节细胞内 K+ 水平方面的基本功能,可能会提供一种具有吸引力但尚未开发的治疗策略。在这里,我们介绍了一类非常规的人工 K+ 转运体,涉及两个 K+ 转运体分子之间的 "运动 "协作。其中,6C6 对 K+ 的 EC50 值高达 0.28 μM(即相对于脂质为 0.28 摩尔%),对 K+/Na+ 的选择性高达 15.5,是迄今为止报道的最具选择性的人工 K+ 转运体之一。最重要的是,我们的研究首次证明了 K+ 选择性人工离子转运体在体外和体内逆转肝纤维化的潜在治疗效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Highly Selective Artificial K+ Transporters Reverse Liver Fibrosis In Vivo

Highly Selective Artificial K+ Transporters Reverse Liver Fibrosis In Vivo
Liver fibrosis is a life-threatening disease that currently lacks clinically effective therapeutic agents. Given the close correlation between dysregulated intracellular K+ homeostasis and the progression of liver fibrosis, developing artificial K+ transporters mimicking the essential function of their natural counterparts in regulating intracellular K+ levels might offer an appealing yet unexplored treatment strategy. Here, we present an unconventional class of artificial K+ transporters involving the “motional” collaboration between two K+ transporter molecules. In particular, 6C6 exhibits an impressive EC50 value of 0.28 μM (i.e., 0.28 mol % relative to lipid) toward K+ and an exceptionally high K+/Na+ selectivity of 15.5, representing one of the most selective artificial K+ transporters reported to date. Most importantly, our study demonstrates, for the first time, the potential therapeutic effect of K+-selective artificial ion transporters in reversing liver fibrosis both in vitro and in vivo.
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