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

• Published in: Renal failure Vol. 44; no. 1; pp. 672 - 681
• Main Authors: Meng, Fanhang, Chen, Qiuyuan, Gu, Shijie, Cui, Ruiwen, Ma, Qing, Cao, Ronghua, Zhao, Ming
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01-12-2022; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: Acute kidney injury; Acute Kidney Injury - chemically induced; Animals; Apoptosis; Apoptosis - genetics; circ-Snrk; Circular RNA; Creatinine; Enzyme-linked immunosorbent assay; Flow cytometry; Gene expression; Hypoxia; Inflammation; Inflammation - genetics; Interleukin 6; ischemia and reperfusion; Kidneys; Kinases; Laboratory Study; MAP kinase; MAPK pathway; MicroRNAs - genetics; Rats; Rats, Sprague-Dawley; RNA, Circular - genetics; RNA, Messenger; Signal transduction; Transcription factors; Tumor necrosis factor-α; MAPK pathway; circ-Snrk; apoptosis; inflammation; ischemia and reperfusion; Acute kidney injury
• ISSN: 0886-022X; 1525-6049
• DOI: 10.1080/0886022X.2022.2032746

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.
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.
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.
Circ-Snrk is involved in AKI development and associated with the MAPK signaling pathway in AKI.