LncRNA IRAR regulates chemokines production in tubular epithelial cells thus promoting kidney ischemia-reperfusion injury

• DOI: 10.1038/s41419-022-05018-x
• Publication Date: 2022-06-22T13:03:21Z
• Authors: Ping Jia; Sujuan Xu; Ting Ren; Tianyi Pan; Xiaoyan Wang; Yunlu Zhang; Zhouping Zou; Man Guo; Qi Zeng; Bo Shen; Xiaoqiang Ding
• Keywords: CXCL1; Proinflammatory cytokine; CXCL2

Abstract Increasing evidence demonstrates that long noncoding RNAs (lncRNAs) play an important role in several pathogenic processes of the kidney. However, functions lncRNAs ischemic acute kidney injury (AKI) remain undefined. In this study, global lncRNA profiling indicated many transcripts were deregulated after ischemia reperfusion (IR). Among them, we identified IRAR (ischemia- r eperfusion a ssociated R NA) as potential candidate, which was mostly expressed by tubular epithelial cells (TECs) IR, involved development AKI. GapmeR-mediated silencing and viral-based overexpression carried out to assess its function contribution IR-induced The results revealed vivo significantly reduced proinflammatory infiltration induced chemokine CCL2, CXCL1 CXCL2 expression both mRNA protein levels TECs, while, resulted downregulation these chemokines. RNA immunoprecipitation pulldown assay validated association between CXCL1/2. Further examination specific ablation CCL2 TECs macrophages cytokine production, attenuated renal dysfunction IR mice. Inhibition CXC receptor 2 (receptor CXCL1/2) neutrofils infiltration, but had no overt effect on function. To explore mechanism upregulation during analyzed promoter region predicted binding site for transcription factor C/EBP β promoter. Silencing TECs. A dual-luciferase reporter chromatin (ChIP) confirmed transcriptional target β. Altogether, our findings identify new player AKI through regulating production immune suggesting is prevention and/or attenuation