Research Paper|Volume 15, Issue 9|pp 3586—3597

miRNA155-5P participated in DDX3X targeted regulation of pyroptosis to attenuate renal ischemia/reperfusion injury

Yan Zhang^1,², Xinghua Lv¹, Qian Fan³, Feng Chen², Zhanhai Wan^1,², Janvier Nibaruta², Hao Wang^1,², Xiaoxia Wang¹, Yuan Yuan², Wenwen Guo², Yufang Leng^1,²

¹Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, Gansu, China
²The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu Province, China
³Tianjin 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

* Co-first author

Received: February 17, 2023Accepted: April 18, 2023Published: May 4, 2023

https://doi.org/10.18632/aging.204692

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.