Forkhead Box Protein K1 Promotes Chronic Kidney Disease by Driving Glycolysis in Tubular Epithelial Cells

• DOI: 10.1002/advs.202405325
• Publication Date: 2024-07-31T15:47:05Z
• Authors: Lu Zhang; Maoqing Tian; Meng Zhang; Chen Li; Xiaofei Wang; Yuyu Long; Yujuan Wang; Jijia Hu; Cheng Chen; Xinghua Chen; Wei Liang; Guohua Ding; Hua Gan; Lunzhi Liu; Huiming Wang
• Keywords: FOXK1; 0303 health sciences; Science; Q; Epithelial Cells; Forkhead Transcription Factors; glycolysis; Mice, Inbred C57BL; Mice; Disease Models, Animal; 03 medical and health sciences; Kidney Tubules; Animals; Humans; transcriptional regulation; phase separation; Renal Insufficiency, Chronic; Glycolysis; chronic kidney disease; Research Article

Renal tubular epithelial cells (TECs) undergo an energy-related metabolic shift from fatty acid oxidation to glycolysis during chronic kidney disease (CKD) progression. However, the mechanisms underlying this burst of remain unclear. Herein, a new critical regulator, transcription factor forkhead box protein K1 (FOXK1) that is expressed in TECs renal fibrosis and exhibits fibrogenic metabolism-rewiring capacities reported. Genetic modification Foxk1 locus alters glycolytic metabolism fibrotic lesions. A surge expression set glycolysis-related genes following FOXK1 activation contributes shift. Nuclear-translocated forms condensate through liquid-liquid phase separation (LLPS) drive target genes. Core intrinsically disordered regions within are mapped validated. therapeutic strategy explored by targeting murine model CKD subcapsular injection recombinant adeno-associated virus 9 vector encoding Foxk1-short hairpin RNA. In summary, mechanism FOXK1-mediated TECs, which involves LLPS enhance transcriptional activity elucidated.