Zhang Qiuping, Liang Qinghong, Wang Guijiang, Xie Xiaopan, Cao Yin, Sheng Nan, Zeng Zhiping, Ren Changliang
State Key Laboratory of Cellular Stress Biology and Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian 361102, China.
Shenzhen Research Institute of Xiamen University, Shenzhen, Guangdong 518057, China.
JACS Au. 2024 Aug 27;4(10):3869-3883. doi: 10.1021/jacsau.4c00521. eCollection 2024 Oct 28.
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, exhibits an impressive EC 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 and .
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。鉴于细胞内钾稳态失调与肝纤维化进展之间的密切关联，开发能够模拟天然钾转运体调节细胞内钾水平基本功能的人工钾转运体，可能提供一种有吸引力但尚未探索的治疗策略。在此，我们展示了一类非常规的人工钾转运体，其涉及两个钾转运体分子之间的“动态”协作。特别是，该转运体对钾表现出令人印象深刻的0.28 μM的EC值（即相对于脂质为0.28 mol%）以及15.5的极高钾/钠选择性，代表了迄今为止报道的最具选择性的人工钾转运体之一。最重要的是，我们的研究首次证明了钾选择性人工离子转运体在体内和体外逆转肝纤维化方面的潜在治疗效果。
