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

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 an...

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Main Authors: Fanhang Meng, Qiuyuan Chen, Shijie Gu, Ruiwen Cui, Qing Ma, Ronghua Cao, Ming Zhao
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:Renal Failure
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/0886022X.2022.2032746
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author Fanhang Meng
Qiuyuan Chen
Shijie Gu
Ruiwen Cui
Qing Ma
Ronghua Cao
Ming Zhao
author_facet Fanhang Meng
Qiuyuan Chen
Shijie Gu
Ruiwen Cui
Qing Ma
Ronghua Cao
Ming Zhao
author_sort Fanhang Meng
collection DOAJ
description 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.
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spelling doaj.art-ecb10d162a3f4ba2a4c761e9897db79d2022-12-22T00:17:31ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492022-12-0144167268110.1080/0886022X.2022.2032746Inhibition of Circ-Snrk ameliorates apoptosis and inflammation in acute kidney injury by regulating the MAPK pathwayFanhang Meng0Qiuyuan Chen1Shijie Gu2Ruiwen Cui3Qing Ma4Ronghua Cao5Ming Zhao6Department of Organ Transplantation, Zhujiang Hospital of Southern Medical University, Guangzhou, ChinaDepartment of Organ Transplantation, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Organ Transplantation, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Organ Transplantation, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Organ Transplantation, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Organ Transplantation, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Organ Transplantation, Zhujiang Hospital of Southern Medical University, Guangzhou, ChinaBackground 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.https://www.tandfonline.com/doi/10.1080/0886022X.2022.2032746Acute kidney injurycirc-SnrkMAPK pathwayischemia and reperfusionapoptosisinflammation
spellingShingle Fanhang Meng
Qiuyuan Chen
Shijie Gu
Ruiwen Cui
Qing Ma
Ronghua Cao
Ming Zhao
Inhibition of Circ-Snrk ameliorates apoptosis and inflammation in acute kidney injury by regulating the MAPK pathway
Renal Failure
Acute kidney injury
circ-Snrk
MAPK pathway
ischemia and reperfusion
apoptosis
inflammation
title Inhibition of Circ-Snrk ameliorates apoptosis and inflammation in acute kidney injury by regulating the MAPK pathway
title_full Inhibition of Circ-Snrk ameliorates apoptosis and inflammation in acute kidney injury by regulating the MAPK pathway
title_fullStr Inhibition of Circ-Snrk ameliorates apoptosis and inflammation in acute kidney injury by regulating the MAPK pathway
title_full_unstemmed Inhibition of Circ-Snrk ameliorates apoptosis and inflammation in acute kidney injury by regulating the MAPK pathway
title_short Inhibition of Circ-Snrk ameliorates apoptosis and inflammation in acute kidney injury by regulating the MAPK pathway
title_sort inhibition of circ snrk ameliorates apoptosis and inflammation in acute kidney injury by regulating the mapk pathway
topic Acute kidney injury
circ-Snrk
MAPK pathway
ischemia and reperfusion
apoptosis
inflammation
url https://www.tandfonline.com/doi/10.1080/0886022X.2022.2032746
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