Research Paper Volume 15, Issue 9 pp 3586—3597
miRNA155-5P participated in DDX3X targeted regulation of pyroptosis to attenuate renal ischemia/reperfusion injury
- 1 Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, Gansu, China
- 2 The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu Province, China
- 3 Tianjin Eye Hospital and Eye Institute, Tianjin Key Lab of Ophthalmology and Visual Science, Nankai University Affiliated Eye Hospital, Nankai Eye Institute, Nankai University, Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, China
Received: February 17, 2023 Accepted: April 18, 2023 Published: May 4, 2023
https://doi.org/10.18632/aging.204692How to Cite
Copyright: © 2023 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Renal ischemia/reperfusion injury (IRI) induced pathological damage to renal microvessels and tubular epithelial cells through multiple factors. However, studies investigated whether miRNA155-5P targeted DDX3X to attenuate pyroptosis were scarce.
Results: The expression of pyroptosis-related proteins (caspase-1, interleukin-1β (IL-1β), NOD-like receptor family pyrin domain containing 3 (NLRP3), and IL-18) were up-regulated in the IRI group. Additionally, miR-155-5p was higher in the IRI group comparing with the sham group. The DDX3X was inhibited by the miR-155-5p mimic more than in the other groups. DEAD-box Helicase 3 X-Linked (DDX3X), NLRP3, caspase-1, IL-1β, IL-18, LDH, and pyroptosis rates were higher in all H/R groups than in the control group. These indicators were higher in the miR-155-5p mimic group than in the H/R and the miR-155-5p mimic negative control (NC) group.
Conclusions: Current findings suggested that miR-155-5p decreased the inflammation involved in pyroptosis by downregulating the DDX3X/NLRP3/caspase-1 pathway.
Methods: Using the models of IRI in mouse and the hypoxia-reoxygenation (H/R)-induced injury in human renal proximal tubular epithelial cells (HK-2 cells), we analyzed the changes in renal pathology and the expression of factors correlated with pyroptosis and DDX3X. Real-time reverse transcription polymerase chain reaction (RT-PCR) detected miRNAs and enzyme-linked immunosorbent assay (ELISA) was used to detect lactic dehydrogenase activity. The StarBase and luciferase assays examined the specific interplay of DDX3X and miRNA155-5P. In the IRI group, severe renal tissue damage, swelling, and inflammation were examined.
Abbreviations
IRI: ischemia/reperfusion injury; I/R: ischemia/reperfusion; AKI: acute kidney injury; ER: endoplasmic reticulum; RBP: RNA-binding protein; DNMT3A: DNA methyltransferase 3A; H/R: hypoxia reoxygenation; ELISA: enzyme-linked immunosorbent assay; LDH: lactate dehydrogenase; HRP: horseradish peroxidase; SD: standard deviation; ANOVA: one-way analysis of variance.