Knockdown of lncRNA TapSAKI alleviates LPS-induced injury in HK-2 cells through the miR-205/IRF3 pathway.

Sepsis is a common and lethal syndrome. Long non-coding RNA (lncRNA) transcript predicting survival in AKI (TapSAKI) has recently been found to serve as an important regulator in sepsis. However, the underlying mechanism of TapSAKI in sepsis pathogenesis remains largely unknown. Our data demonstrated that lipopolysaccharide (LPS)-induced HK-2 cell injury by weakening cell viability and enhancing cell apoptosis and inflammation. TapSAKI was upregulated and miR-205 was downregulated in LPS-induced HK-2 cells. TapSAKI knockdown or miR-205 overexpression alleviated LPS-induced cytotoxicity in HK-2 cells. TapSAKI sequestered miR-205 via acting as a miR-205 sponge. Moreover, the mitigating effect of TapSAKI silencing on LPS-induced HK-2 cell injury was mediated by miR-205. Additionally, the interferon regulatory factor 3 (IRF3) signaling was involved in the regulation of the TapSAKI/miR-205 axis on LPS-induced HK-2 cell damage. Our current study suggested that TapSAKI silencing relieved LPS-induced injury in HK-2 cells at least in part by sponging miR-205 and regulating the IRF3 signaling pathway, highlighting a novel understanding for sepsis pathogenesis and a promising target for this disease treatment.

LncRNA TapSAKI promotes inflammation injury in HK-2 cells and urine derived sepsis-induced kidney injury.

OBJECTIVE: To explore the possible mechanism of lncRNA TapSAKI in urine derived sepsis-induced kidney injury. MATERIALS AND METHODS: In vivo urine-derived sepsis (US) rat model and in vitro LPS-induced HK-2 cells were established, and TapSAKI, miR-22, PTEN, TLR4 and p-p65 expressions were detected by qRT-PCR and western blot. RNA precipitation and RNA pull-down were performed to confirm the interaction between TapSAKI and miR-22. RESULTS: TapSAKI was up-regulated, miR-22 was down-regulated, PTEN, TLR4 and p-p65 expressions, and inflammatory factors TNF-α and IL-6 levels were up-regulated in kidney tissue of US rats and LPS-induced HK-2 cells. In addition, TapSAKI interacted with miR-22, and negatively modulate miR-22 expression. We also observed TapSAKI promoted PTEN expression, TLR4/NF-κB pathway related proteins TLR4 and p-p65, and apoptosis protein cleaved-caspase-3 through negatively regulating miR-22. Further experiments proved TapSAKI/miR-22/TLR4/NF-κB pathway could promote HK-2 cell apoptosis. Finally, in vivo experiments showed TapSAKI knockdown negatively regulated miR-22 and positively regulate PTEN, decreased renal function indicators blood urea nitrogen and serum creatinine, and reduced TNF-α and IL-6. CONCLUSION: TapSAKI was elevated in urine derived sepsis-induced kidney injury, and promoted HK-2 cell apoptosis and inflammatory response through miR-22/PTEN/TLR4/NF-κB pathway.