GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE301nnn/GSE301865/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301865GEOGSEfalseEffect of TNFSF14 deficiency on ischemia/reperfusion induced acute kidney injury in miceLIGHT (homologous to lymphotoxins) exhibits inducible expression and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes, also called TNFSF14 (tumor necrosis factor family member 14), or CD258, a novel member of the TNF superfamily. Our study demonstrated upregulated expression levels of TNFSF14 and its receptors (LTβR and HVEM) in kidney tissues of I/R-AKI mice, consistent with results of clinical AKI patients. To address this, LIGHT+/+ and LIGHT-/- mice underwent bilateral renal ischamia/reperfusion operation. LIGHT deficiency remarkably attenuated I/R-AKI, as evidenced by rescued renal function, ameliorated tubular cell apoptosis, and alleviated inflammatory responses. Consistently, blocking LIGHT signaling with its soluble receptor fusion proteins (HVEM-IgG-Fc or LTβR-IgG-Fc) improved I/R renal dysfunction. RNA-sequencing and corresponding results indicated that LIGHT promoted oxidative stress and inflammation triggered by ischemic injury. Mechanistically, LIGHT promoted mitochondrial fission by enhancing Drp1 phosphorylation (Ser616) and its translocation to the mitochondria. In conclusion, these results suggest that LIGHT-HVEM/LTβR signaling is critical for the I/R-AKI pathogenesis and it is further confirmed to be related to the increase in I/R-induced oxidative stress and mitochondria dysfunction, which may be the underlying mechanism of LIGHT signaling-mediated I/R-AKI.2026/05/20GSE301865GSM9090988GSM9090989GSM9090993GSM9090991GSM9090992GSM909099021103301865Mus musculus