Acute kidney injury (AKI) is a common clinical problem, and patients who survive AKI have a high risk of chronic kidney disease (CKD). The mechanism of CKD post-AKI, characterized by progressive renal fibrosis, is still unclear. Maladaptive tubular epithelial cells (TECs) after AKI are considered a leading cause of renal fibrosis post-AKI. TECs under maladaptive repair manifest characteristics of senescence. Removing senescent TECs by genetic ablation has been proven effective in reducing renal fibrosis. Senolytics, which eliminate senescent cells by pharmacological intervention, have been studied in a series of degenerative diseases. To our knowledge, the effects of senolytics on renal fibrosis post-AKI have not been verified before. Here, we confirmed renal senescence in the unilateral ischemia/reperfusion injury murine model. Senescent TECs could activate fibroblasts and senolytics specifically induced apoptosis of senescent TECs. Next, we demonstrated that senolytics could reduce renal senescence and ameliorate renal fibrosis in both unilateral renal ischemia/reperfusion injury and multiple-cisplatin-treatment murine models. Our results indicate senescent TECs as a vital factor in renal fibrosis progression, and senolytic therapy might be promising for treating CKD post-AKI.
Keywords: acute kidney injury; chronic kidney disease; dasatinib; quercetin; senescence; senolytics.
© 2020 Federation of American Societies for Experimental Biology.