p53/sirtuin 1/NF-κB Signaling Axis in Chronic Inflammation and Maladaptive Kidney Repair After Cisplatin Nephrotoxicity

• DOI: 10.3389/fimmu.2022.925738
• Publication Date: 2022-07-07T09:54:17Z
• Authors: Ying Fu; Ying Wang; Yuxue Liu; Chengyuan Tang; Juan Cai; Guochun Chen; Zheng Dong
• Keywords: Sirtuin 1; Nephrotoxicity; IκBα

Chronic inflammation contributes to maladaptive kidney repair, but its regulation is unclear. Here, we report that sirtuin 1 (SIRT1) downregulated after repeated low-dose cisplatin (RLDC) injury, and this downregulation leads p65 acetylation consequent NF-κB activation resulting in a persistent inflammatory response. RLDC induced the down-regulation of SIRT1 NF-κB, which were accompanied by chronic tubular damage, tubulointerstitial inflammation, fibrosis mice. Inhibition suppressed production pro-inflammatory cytokines fibrotic phenotypes RLDC-treated renal cells. agonists markedly reduced (a key component NF-κB), attenuation responses. Conversely, knockdown exacerbated these cellular changes. At upstream, p53 was activated treatment repress SIRT1, acetylation, transcription cytokines. In mice, attenuated RLDC-induced tissue fibrosis. Together, results unveil p53/SIRT1/NF-κB signaling axis repair following treatment, where represses increase for activation, leading inflammation.