Inhibition of Circ-Snrk ameliorates apoptosis and inflammation in acute kidney injury by regulating the MAPK pathway. Issue 1 (31st December 2022)

• Record Type: Journal Article
• Authors: Meng, Fanhang; Chen, Qiuyuan; Gu, Shijie; Cui, Ruiwen; Ma, Qing; Cao, Ronghua; Zhao, Ming
• Is Part Of: Renal failure. Volume 44:Issue 1(2022)
• Page Start: 672
• Page End: 681
• Publication Date: 2022-12-31
• Subjects: Acute kidney injury -- circ-Snrk -- MAPK pathway -- ischemia and reperfusion -- apoptosis -- inflammation; Chronic renal failure -- Periodicals; Acute renal failure -- Periodicals; Uremia -- Periodicals; 616.614005
• DOI: 10.1080/0886022X.2022.2032746
• Languages: English
• ISSNs: 0886-022X

Abstract

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.