Highly Selective Artificial K<sup>+</sup> Transporters Reverse Liver Fibrosis In Vivo
Qiuping Zhang, Qinghong Liang, Guijiang Wang, Xiaopan Xie, Yin Cao, Nan Sheng, Zhiping Zeng, Changliang Ren
Abstract
High Resolution Image Download MS PowerPoint Slide 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 EC 50 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 .