Inhibition of Circ-Snrk ameliorates apoptosis and inflammation in acute kidney injury by regulating the MAPK pathway

Abstract

Background Circular RNA (circRNA) is involved in the process of acute kidney injury (AKI), but only a few circRNAs have been reported. In the study, we investigated a new circRNA and its association with AKI. Methods An AKI model was established in Sprague-Dawley rats, followed by serum creatinine and urea nitrogen tests measured by a biochemical analyzer. The pathological changes and apoptosis in the renal tissue were detected by Hematoxylin and Eosin, and TUNEL staining. Then, circRNA expression in AKI was determined by quantitative real-time-PCR (qRT-PCR). NRK-52E cells were induced with hypoxia/reoxygenation (H/R) as in vitro models and the circ-Snrk level was tested by qRT-PCR. The effects of circ-Snrk in H/R-induced NRK-52E cells were assessed by flow cytometry, western blot, and enzyme-linked immunosorbent assay. Finally, RNA sequencing and western blot analysis were used to validate the mRNA profile and pathways involved in circ-Snrk knockdown in H/R-induced NRK-52E. Results A reliable AKI rat model and H/R cell model were established. qRT-PCR demonstrated that circ-Snrk level was upregulated in AKI left kidney tissue and NRK-52E cells with H/R treatment. Circ-Snrk knockdown inhibited apoptosis of NRK-52E cells and secretion of inflammatory factors (IL-6 and TNF-α). RNA sequencing showed that the mRNA profile changed after inhibition of circ-Snrk and differential expression of mRNA mainly enriched various signaling pathways, including MAPK signaling pathway. Furthermore, western blot indicated that circ-Snrk knockdown could inhibit the activation of p-JNK and p-38 transcription factors. Conclusions Circ-Snrk is involved in AKI development and associated with the MAPK signaling pathway in AKI.

CircRNA_45478 promotes ischemic AKI by targeting the miR ‐190a‐5p/ PHLPP1 axis

“…Two studies found that CircRNAs mediated the development of ischemic AKI 15,16 . In the current study, we demonstrated that circRNA_45478 promoted renal cell apoptosis during ischemic injury.…”

“…Two studies reported that circ-Snrk and mmu_circ_0000943 mediated the development of ischemic AKI. 15,16 Between them, circ-Snrk mediated the renal cell apoptosis during ischemic injury. 15 In the present study, we showed that cir-cRNA_45478 was an apoptosis driver during ischemic injury, which was supported by the following evidences:…”

“…Presently, only a few studies have focused on the role of circRNAs in ischemic AKI. Two studies reported that circ‐Snrk and mmu_circ_0000943 mediated the development of ischemic AKI 15,16 . Between them, circ‐Snrk mediated the renal cell apoptosis during ischemic injury 15 .…”

“…CircRNAs usually act as competing endogenous RNA (ceRNA) to regulate microRNA (miRNA) expression 14 . Recently, two studies suggested that circular RNAs (circRNAs) could mediate the progression of ischemic AKI 15,16 . One study reported that Circ‐Snrk mediated the apoptosis and inflammation in ischemic AKI via activation of p38MAPK and p‐JNK signal pathways 15 .…”

Circular RNAs in Acute Kidney Injury: Roles in Pathophysiology and Implications for Clinical Management

“…NRK-52E rat kidney epithelial cells exposed to hypoxia and reperfusion showed increased expression of circ-SNRK, which was shown to participate in the activation of the MAPK signalling pathway and promoting cell apoptosis and secretion of TNF-α and IL-6. Knockdown of circ-SNRK resulted in the reduction in renal inflammation and improvement in the serum creatinine and urea levels [ 50 ]. Conversely, circ-YAP1 was downregulated in AKI patients and in HK-2 cells subjected to IRI conditions.…”