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MicroRNA-141-3p attenuates oxidative stress-induced hepatic ischemia reperfusion injury via Keap1/Nrf2 pathway

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Abstract

Background

Hepatic ischemia reperfusion injury (IRI) is a major factor affecting the prognosis of liver transplantation through a series of severe cell death and inflammatory responses. However, the potential role of miR-141-3p in hepatic IRI is currently unknown.

Methods

We collected the serum of liver transplantation patients to study the relationship between miR-141-3p and liver injury. A mouse hepatic IRI model was established to measure hepatic dysfunction and cell apoptosis. MiR-141-3p mimic and inhibitor were transfected into hepatocytes to explore the characteristics of hypoxia/reoxygenation (H/R), a classical hepatic IRI in vitro model.

Results

We found that miR-141-3p levels were negatively correlated with alanine aminotransferase (ALT)/aspartate aminotransferase (AST) in liver transplantation patients. The results demonstrated that miR-141-3p was decreased in mouse liver tissue after hepatic IRI in mice and in hepatocytes after H/R. Overexpression of miR-141-3p directly decreased Kelch-like ECH-associated protein 1 (Keap1) levels and attenuated cell apoptosis in vivo and in vitro, while inhibition of miR-141-3p facilitated apoptosis. Further experiments revealed that overexpression of miR-141-3p also attenuated oxidative stress-induced damage in hepatocytes under H/R conditions.

Conclusions

Our results indicate that miR-141-3p plays a major role in hepatic IRI through the Keap1 signaling pathway, and the present study suggests that miR-141-3p might have a protective effect on hepatic IRI to some extent.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant Nos. 81873592, 81703063); the graduate tutor team construction project of Chongqing Municipal Education Commission Foundation, China (Grant No. dstd201801); and the Natural Science Foundation of Chongqing, China (Grant No. cstc2018jscx-msybX0133).

Funding

This work was supported by the National Natural Science Foundation of China (Grant Nos. 81873592, 81703063); the graduate tutor team construction project of Chongqing Municipal Education Commission Foundation, China (Grant No. dstd201801); and the Natural Science Foundation of Chongqing, China (Grant No. cstc2018jscx-msybX0133).

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Author notes

  1. Xufu Wei and Zhongjun Wu have contributed equally to this work and share senior authorship.

Authors and Affiliations

  1. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 YouYi Road, YuZhong District, Chongqing, 400016, China

    Tingting Li, Qingsong Chen, Jiangwen Dai, Zuotian Huang, Yunhai Luo, Tong Mou, Junliang Pu, Hang Yang, Xufu Wei & Zhongjun Wu

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  1. Tingting Li
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Contributions

ZW and TL participated in designing the experiments and editing the article. TL, XW and QC participated in the collection of samples. TL, QC, JD, ZH, YL, JP and HY participated in performing the studies. TL, ZH and TM wrote the manuscript.

Corresponding author

Correspondence to Zhongjun Wu.

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The authors declare that there are no conflicts of interest.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Li, T., Chen, Q., Dai, J. et al. MicroRNA-141-3p attenuates oxidative stress-induced hepatic ischemia reperfusion injury via Keap1/Nrf2 pathway. Mol Biol Rep 49, 7575–7585 (2022). https://doi.org/10.1007/s11033-022-07570-3

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