Overexpression of MiR-188-5p Downregulates IL6ST/STAT3/ NLRP3 Pathway to Ameliorate Neuron Injury in Oxygen-glucose Deprivation/Reoxygenation
- Authors: Hu Y.1, Wang G.2, Yang G.1
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Affiliations:
- Department of Neurology, Central South University Xiangya School of Medicine Affiliated Haikou Hospital
- Department of Neurology,, Central South University Xiangya School of Medicine Affiliated Haikou Hospital,
- Issue: Vol 21, No 3 (2024)
- Pages: 263-273
- Section: Medicine
- URL: https://gynecology.orscience.ru/1567-2026/article/view/644404
- DOI: https://doi.org/10.2174/0115672026313555240515103132
- ID: 644404
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Abstract
Background:CI/R, characterized by ischemic injury following abrupt reestablishment of blood flow, can cause oxidative stress, mitochondrial dysfunction, and apoptosis. We used oxygen-glucose deprivation/reoxygenation (OGD/R) induced injury in HT22 and primary mouse cortical neurons (MCN) as a model for CI/R.
Objective:This study investigates the role of miR-188-5p in hippocampal neuron cell injury associated with Cerebral Ischemia-Reperfusion (CI/R).
Methods:HT22 and MCN cells were induced by OGD/R to construct an in vitro model of CI/R. Cell apoptosis and proliferation were assessed using flow cytometry and the Cell Counting Kit-8 (CCK8). ELISA was conducted to measure the levels of IL-1β, IL-6, and TNF-α. Moreover, the interaction between miR-188-5p and IL6ST was investigated using dual luciferase assay, the expression of miR-188-5p, Bax, cleaved-caspase3, IL-6, Bcl-2, IL-1β, TNF-α, IL6ST, NFκB, NLRP3 and STAT3 was evaluated using RT-qPCR or Western blot, and immunofluorescence was used to analyze the co-expression of p-STAT3 and NLRP3 in neuronal cells.
Results:OGD/R reduced proliferation and miR-188-5p levels and increased IL6ST expression, inflammation, and apoptosis in HT22 and MCN cells. Moreover, miR-188-5p was found to bind to IL6ST. Mimics of miR-188-5p reduced apoptosis, lowered the expression of cleaved-caspase3 and Bax proteins, and elevated Bcl-2 protein expression in cells treated with OGD/R. Overexpression of miR-188-5p decreased the levels of NLRP3 and p-STAT3 in the OGD/R group. Furthermore, the overexpression of miR-188-5p reduced IL6ST, p- NFκB/NFκB, p-STAT3/STAT3, and NLRP3 proteins in OGD/R, and these effects could be reversed by IL6ST overexpression.
Conclusion:Mimics of miR-188-5p were found to inhibit inflammation and the STAT3/NLRP3 pathway via IL6ST, thereby ameliorating injury in HT22 and MCN cells treated with OGD/R in the context of CI/R.
About the authors
Yujie Hu
Department of Neurology, Central South University Xiangya School of Medicine Affiliated Haikou Hospital
Email: info@benthamscience.net
Ganlan Wang
Department of Neurology,, Central South University Xiangya School of Medicine Affiliated Haikou Hospital,
Email: info@benthamscience.net
Guoshuai Yang
Department of Neurology, Central South University Xiangya School of Medicine Affiliated Haikou Hospital
Author for correspondence.
Email: info@benthamscience.net
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