The prediction of mortality for septic acute kidney injury (AKI) has been assessed by a number of potential biomarkers, including long noncoding RNAs (lncRNAs). However, the validation of lncRNAs as biomarkers, particularly for the early stages of septic AKI, is still warranted. Our results indicate that the lncRNA TCONS_00016233 is upregulated in plasma of sepsis-associated non-AKI and AKI patients, but a higher cutoff threshold (9.5 × 10⁵, copy number) provided a sensitivity of 71.9% and specificity of 89.6% for the detection of AKI. The plasma TCONS_00016233 was highly correlated with serum creatinine, tissue inhibitor metalloproteinase-2 (TIMP-2), insulin-like growth factor binding protein-7 (IGFBP7), interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), C-reactive protein (CRP), and urinary TCONS_00016233. Lipopolysaccharide (LPS) induced the expression of lncRNA TCONS_00016233 via the Toll-like receptor 4 (TLR4)/p38 mitogen-activated protein kinase (MAPK) signal pathway in human renal tubular epithelial (HK-2) cells. Furthermore, TCONS_00016233 mediates the LPS-induced HK-2 cell apoptosis and the expression of IL-1β and TNF-α. Mechanistically, TCONS_00016233 acts as a competing endogenous RNA (ceRNA) to prevent microRNA (miR)-22-3p-mediated downregulation of the apoptosis-inducing factor mitochondrion-associated 1 (AIFM1). Finally, overexpression of TCONS_00016233 is capable of aggravating the LPS- and cecal ligation and puncture (CLP)-induced septic AKI by targeting the miR-22-3p/AIFM1 axis. Taken together, our data indicate that TCONS_00016233 may serve as an early diagnosis marker for the septic AKI, possibly acting as a novel therapeutic target for septic AKI.

对败血性急性肾损伤（AKI）死亡率的预测已通过许多潜在的生物标记进行了评估，包括长的非编码RNA（lncRNA）。但是，仍然有必要对lncRNA作为生物标记物进行验证，特别是对于败血性AKI的早期阶段。我们的结果表明，败血症相关的非AKI和AKI患者血浆中的lncRNA TCONS_00016233被上调，但截止阈值较高（9.5×10 ⁵，拷贝数）对AKI的检测灵敏度为71.9％，特异性为89.6％。血浆TCONS_00016233与血清肌酐，组织抑制剂金属蛋白酶2（TIMP-2），胰岛素样生长因子结合蛋白7（IGFBP7），白介素1β（IL-1β），肿瘤坏死因子α（TNF- α），C反应蛋白（CRP）和尿液TCONS_00016233。脂多糖（LPS）通过Toll样受体4（TLR4）/ p38丝裂原活化蛋白激酶（MAPK）信号途径诱导人肾小管上皮细胞（HK-2）中lncRNA TCONS_00016233的表达。此外，TCONS_00016233介导了LPS诱导的HK-2细胞凋亡以及IL-1β和TNF-α的表达。机械上，TCONS_00016233充当竞争性内源RNA（ceRNA），以防止microRNA（miR）-22-3p介导的凋亡诱导因子线粒体相关1（AIFM1）的下调。最后，通过靶向miR-22-3p / AIFM1轴，TCONS_00016233的过表达能够加重LPS和盲肠结扎和穿刺（CLP）诱导的败血性AKI。综上所述，我们的数据表明TCONS_00016233可以作为败血症AKI的早期诊断标记，可能充当败血症AKI的新型治疗靶标。