Progressive Cellular Senescence Mediates Renal Dysfunction in Ischemic Nephropathy

• Published in: Journal of the American Society of Nephrology Vol. 32; no. 8; pp. 1987 - 2004
• Main Authors: Kim, Seo Rin, Puranik, Amrutesh S., Jiang, Kai, Chen, Xiaojun, Zhu, Xiang-Yang, Taylor, Ian, Khodadadi-Jamayran, Alireza, Lerman, Amir, Hickson, LaTonya J., Childs, Bennett G., Textor, Stephen C., Tchkonia, Tamara, Niewold, Timothy B., Kirkland, James L., Lerman, Lilach O.
• Format: Journal Article
• Language: English
• Published: United States American Society of Nephrology 01.08.2021
• Subjects: Animals; Apoptosis - drug effects; Basic Research; Caspase 8 - metabolism; Cellular Senescence - drug effects; Cellular Senescence - genetics; Cellular Senescence - physiology; Chronic Disease; Cyclin-Dependent Kinase Inhibitor p16 - genetics; Cyclin-Dependent Kinase Inhibitor p16 - metabolism; Cyclin-Dependent Kinase Inhibitor p19 - metabolism; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Dasatinib - pharmacology; Disease Models, Animal; Enzyme Activation - drug effects; Epithelial Cells - physiology; Epithelial-Mesenchymal Transition; Gene Expression; Heparin-binding EGF-like Growth Factor - genetics; Humans; Ischemia - etiology; Ischemia - physiopathology; Kidney - blood supply; Kidney - pathology; Kidney - physiopathology; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Osteopontin - genetics; p21-Activated Kinases - genetics; p21-Activated Kinases - metabolism; Protein Kinase Inhibitors - pharmacology; Renal Artery Obstruction - complications; Renal Insufficiency, Chronic - etiology; Renal Insufficiency, Chronic - pathology; Renal Insufficiency, Chronic - physiopathology; Sequence Analysis, RNA; Single-Cell Analysis; Tacrolimus - analogs & derivatives; Tacrolimus - pharmacology; Up-Regulation; senescence; quercetin; renal artery stenosis; dasatinib; transcriptome

Significance Statement Renal artery stenosis (RAS) engenders stenotic-kidney ischemia, dysfunction, and injury, but whether these are mediated by cellular senescence has not been elucidated. INK-ATTAC transgenic mice, high-resolution imaging, and unbiased single-cell RNA sequencing of murine kidneys...