LncRNA HOX transcript antisense RNA accelerated kidney injury induced by urine-derived sepsis through the miR-22/high mobility group box 1 pathway

Abstract Objective This study investigated the role of long noncoding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) in kidney injury induced by urine-derived sepsis (US). Materials and methods An Escherichia coli suspension was injected into the distal ureter of adult male Sprague Dawley rats to establish a US model. Lipopolysaccharides (LPSs) were used to induce an in vitro septic model. The interaction between HOTAIR and microRNA 22 (miR-22) was detected by RNA precipitation and RNA pull-down assays. The expression of HOTAIR, miR-22, and high mobility group box 1 (HMGB1) were detected by quantitative real time polymerase chain reaction (qRT-PCR) and Western blot analyses. Results Compared with a sham group, HOTAIR was upregulated in kidney tissues of the US group. HOTAIR was also upregulated in LPS-induced human renal tubular epithelial cells (HK-2). Furthermore, HOTAIR negatively regulated miR-22 and promoted apoptosis of HK-2 cells. HOTAIR also promoted HMGB1 expression and HK-2 cell apoptosis by inhibiting miR-22. In addition, the miR-22/HMGB1 pathway was involved in LPS-induced HK-2 cell apoptosis. In vivo experiments showed that HOTAIR negatively modulated miR-22 and positively modulated HMGB1 and that HOTAIR knockdown decreased renal function indicators (blood urea nitrogen [BUN] and serum creatinine). Conclusion HOTAIR was upregulated in sepsis-induced kidney injury, which promoted HK-2 cell apoptosis in kidney injury through the miR-22/HMGB1 pathway.