Circ_0001818 targets miR-136-5p to increase lipopolysaccharide-induced HK2 cell injuries by activating TXNIP/NLRP3 inflammasome pathway

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  • 作者:Kuang Feng, Wang Baiqi, You Ting, Liu Yu, Li Pei, Wang Jian
  • 期刊:SHOCK
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Background The implication of circular RNAs (circRNAs) in sepsis -related complications arouses much attention, which provides additional treatment options for sepsis -related complications. The purpose of this study is to unveil the function and functional mechanism of circ_0001818 in cell models of septic acute kidney injury (AKI). Methods Septic AKI cell models were constructed using HK2 cells treated with lipopolysaccharide (LPS). The expression levels of circ_0001818 , miR-136-5p and thioredoxin interacting protein ( TXNIP ) mRNA were examined by quantitative real-time PCR (qPCR). Cell viability and death were explored by CCK-8 and flow cytometry assays. The activity of oxidative stress-related markers was examined using commercial kits. The secretion of inflammatory factors was examined using ELISA kits. The binding between miR-136-5p and circ_0001818 or TXNIP was validated by dual-luciferase reporter test and pull-down assay. The receiver operating characteristic (ROC) curve was depicted to assess the diagnostic value of circ_0001818 , miR-136-5p and TXNIP in serumal exosomes from patients with septic AKI. Results Circ_0001818 expression was elevated in LPS-treated HK2 cells. Loss-of-function assays displayed that circ_0001818 downregulation alleviated LPS-induced HK2 cell death, oxidative stress, inflammatory release and inflammasome activation. MiR-136-5p was targeted by circ_0001818 , and inhibition of miR-136-5p attenuated the effects of circ_0001818 downregulation, thus recovering LPS-induced HK2 cell injuries. MiR-136-5p targeted the downstream TXNIP , and circ_0001818 dysregulation could affect TXNIP expression via targeting miR-136-5p . Overexpression of TXNIP overturned the effects of circ_0001818 downregulation. Moreover, circ_0001818 , miR-136-5p and TXNIP in serumal exosomes had diagnostic values. Conclusion Circ_0001818 targets miR-136-5p to activate TXNIP expression, leading to the contribution of LPS-induced HK2 cell injury.

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