Downregulation of circ‐ZNF644 alleviates LPS‐induced HK2 cell injury via miR‐335‐5p/HIPK1 axis

Abstract

Circular RNA (circRNA) has been confirmed to be involved in regulating sepsis‐induced acute kidney injury (AKI). Our research aims to explore circ‐ZNF644 role in the development of sepsis‐induced AKI. Lipopolysaccharide (LPS) was used to induce kidney tubular epithelial cell (HK2) injury. ELISA assay was performed to measure the concentrations of inflammation factors. Cell functions were determined by cell counting kit 8 assay, EdU assay and flow cytometry. Protein expression was evaluated by Western blot analysis. Quantitative real‐time PCR was used to detect relative expression of circ‐ZNF644, miR‐335‐5p and homeodomain‐interacting protein kinase 1 (HIPK1). RNA interaction was confirmed by dual‐luciferase reporter assay and RIP assay. LPS enhanced HK2 cell inflammation, oxidative stress, apoptosis, and reduced proliferation. Circ‐ZNF644 was overexpressed in sepsis‐induced AKI patients. Circ‐ZNF644 knockdown suppressed LPS‐induced HK2 cell injury, and this effect could be revoked by miR‐335‐5p inhibitor. MiR‐335‐5p was sponged by circ‐ZNF644, and its expression was downregulated in sepsis‐induced AKI patients. HIPK1 was targeted by miR‐335‐5p, and its expression could be suppressed by circ‐ZNF644 knockdown. MiR‐335‐5p had an inhibition effect on HK2 cell injury induced by LPS, and HIPK1 overexpression could reverse this effect. Circ‐ZNF644 knockdown relieved LPS‐induced HK2 cell injury through the miR‐335‐5p/HIPK1 axis, confirming that circ‐ZNF644 contributed to sepsis‐induced AKI.

Inhibition of sepsis‐induced acute kidney injury via thecircITCH‐miR‐579‐3p‐ZEB2axis

“…Increasing studies constructed cell models of sepsis‐induced AKI in renal cells with the treatment of lipopolysaccharide (LPS) and claimed that apoptosis and inflammatory response were associated events in AKI, 5,6 which were driven by various molecules, including non‐coding RNAs 7,8 . CircRNAs comprise non‐coding RNAs with closed ring structure, which are widely found in eukaryotes and involved in biological processes, such as tumorigenesis, apoptosis, and inflammation 9–11 .…”

Circ_0040994 depletion alleviates lipopolysaccharide‐induced HK2 cell injury through miR‐17‐5p/TRPM7 axis

“…Lipopolysaccharide (LPS) is a classical inducer of acute inflammation and commonly binds to transmembrane toll‐like receptor 4 to mediate inflammatory process 7,8 . LPS can induce inflammation and oxidative stress response 9,10 . Therefore, we treated human kidney‐2 (HK2) cells with LPS to establish AKI cell models 11 to explore the latent mechanisms of AKI.…”

“…7,8 LPS can induce inflammation and oxidative stress response. 9,10 Therefore, we treated human kidney-2 (HK2) cells with LPS to establish AKI cell models 11 to explore the latent mechanisms of AKI.…”

JMJD3 downregulates IL4i1 aggravating lipopolysaccharide‐induced acute lung injury via H3K27 and H3K4 demethylation

“…Gram‐negative bacilli infection in alveolus or interstitials is the leading cause of ALI 2 . Endotoxin secreted by bacteria, mainly lipopolysaccharide (LPS), has a potent pro‐inflammatory potential, which could lead to ALI 3,4 . It damages the alveolar‐capillary membrane and causes life‐threatening pneumonia 5 by activating the toll‐like receptor 4 (TLR4)‐nuclear factor‐kappa B (NF‐κB) pathway 6,7 …”

“…Macrophages play a central role in the host defense against pathogens 3 . Depending on the diversity of the microenvironments and stimulation, macrophages could polarize into the pro‐inflammatory M1 phenotype or anti‐inflammatory M2 phenotype 8 .…”