{"title":"高选择性人工 K+ 转运体逆转体内肝纤维化","authors":"Qiuping Zhang, Qinghong Liang, Guijiang Wang, Xiaopan Xie, Yin Cao, Nan Sheng, Zhiping Zeng, Changliang Ren","doi":"10.1021/jacsau.4c00521","DOIUrl":null,"url":null,"abstract":"Liver fibrosis is a life-threatening disease that currently lacks clinically effective therapeutic agents. Given the close correlation between dysregulated intracellular K<sup>+</sup> homeostasis and the progression of liver fibrosis, developing artificial K<sup>+</sup> transporters mimicking the essential function of their natural counterparts in regulating intracellular K<sup>+</sup> levels might offer an appealing yet unexplored treatment strategy. Here, we present an unconventional class of artificial K<sup>+</sup> transporters involving the “motional” collaboration between two K<sup>+</sup> transporter molecules. In particular, <b>6C6</b> exhibits an impressive EC<sub>50</sub> value of 0.28 μM (i.e., 0.28 mol % relative to lipid) toward K<sup>+</sup> and an exceptionally high K<sup>+</sup>/Na<sup>+</sup> selectivity of 15.5, representing one of the most selective artificial K<sup>+</sup> transporters reported to date. Most importantly, our study demonstrates, for the first time, the potential therapeutic effect of K<sup>+</sup>-selective artificial ion transporters in reversing liver fibrosis both <i>in vitro</i> and <i>in vivo</i>.","PeriodicalId":14799,"journal":{"name":"JACS Au","volume":"36 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Highly Selective Artificial K+ Transporters Reverse Liver Fibrosis In Vivo\",\"authors\":\"Qiuping Zhang, Qinghong Liang, Guijiang Wang, Xiaopan Xie, Yin Cao, Nan Sheng, Zhiping Zeng, Changliang Ren\",\"doi\":\"10.1021/jacsau.4c00521\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Liver fibrosis is a life-threatening disease that currently lacks clinically effective therapeutic agents. Given the close correlation between dysregulated intracellular K<sup>+</sup> homeostasis and the progression of liver fibrosis, developing artificial K<sup>+</sup> transporters mimicking the essential function of their natural counterparts in regulating intracellular K<sup>+</sup> levels might offer an appealing yet unexplored treatment strategy. Here, we present an unconventional class of artificial K<sup>+</sup> transporters involving the “motional” collaboration between two K<sup>+</sup> transporter molecules. In particular, <b>6C6</b> exhibits an impressive EC<sub>50</sub> value of 0.28 μM (i.e., 0.28 mol % relative to lipid) toward K<sup>+</sup> and an exceptionally high K<sup>+</sup>/Na<sup>+</sup> selectivity of 15.5, representing one of the most selective artificial K<sup>+</sup> transporters reported to date. Most importantly, our study demonstrates, for the first time, the potential therapeutic effect of K<sup>+</sup>-selective artificial ion transporters in reversing liver fibrosis both <i>in vitro</i> and <i>in vivo</i>.\",\"PeriodicalId\":14799,\"journal\":{\"name\":\"JACS Au\",\"volume\":\"36 1\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-08-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JACS Au\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1021/jacsau.4c00521\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JACS Au","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1021/jacsau.4c00521","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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.