Acute Kidney Injury

Circ_0068[Circular RNA]

miR-21-5p[miRNA]

LPS[mRNA]

HK-2 cells

Homo sapiens (human)

Biochem Biophys Res Commun. 2021 Feb 12;540:1-7. doi: 10.1016/j.bbrc.2020.12.018. Epub 2021 Jan 8.

Circular RNA circ_0068,888 protects against lipopolysaccharide-induced HK-2 cell injury via sponging microRNA-21-5p.

qRT-PCR

Our previous findings revealed that hsa_circ_0068,888 was markedly down-regulated in the plasma of patients with sepsis-associated acute kidney injury (AKI). However, its molecular mechanism in AKI remains unclear. Herein, we explored the role of hsa_circ_0068,888 in AKI. Human renal proximal tubular cell line HK-2 was stimulated with lipopolysaccharide (LPS) to mimic AKI in vitro. Decreased hsa_circ_0068,888 expression was observed in AKI cell model. The overexpression of hsa_circ_0068,888 significantly increased the viability of LPS-stimulated HK-2 cells, whereas hsa_circ_0068,888 downregulation showed the opposite effect. Furthermore, LPS triggered inflammatory response and oxidative stress, which was inhibited by hsa_circ_0068,888 overexpression and enhanced by hsa_circ_0068,888 down-regulation. Hsa_circ_0068,888 overexpression suppressed the activation of nuclear factor-κB (NF-κB) pathway triggered by LPS as evidenced by decreased p-p65 protein level and nuclear translocation of p65 in hsa_circ_0068,888 overexpressed cells. Additionally, we proved that hsa_circ_0068,888 targeted microRNA-21-5p (miR-21-5p). The expression of miR-21-5p was markedly increased and was negatively regulated by hsa_circ_0068,888 in LPS-stimulated HK-2 cells. Furthermore, we demonstrated that miR-21-5p overexpression reversed the effects on cell viability, inflammatory response, oxidative stress, and NF-κB pathway induced by hsa_circ_0068,888 overexpression in LPS-stimulated HK-2 cells. Overall, these results implied that hsa_circ_0068,888 shows a protective effect on AKI by sponging miR-21-5p. Hence, up-regulation of hsa_circ_0068,888 might be a potential strategy in treatment for AKI.