Research Paper Volume 16, Issue 2 pp 1352—1373
MicroRNA-141-3p reduces pulmonary hypoxia/reoxygenation injury through suppression of Beclin-1-dependent autophagy
- 1 Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, P.R. China
- 2 Jiangxi Maternal and Child Health Hospital, Nanchang 330006, P.R. China
- 3 Nanchang University, Nanchang 330006, P.R. China
Received: May 26, 2023 Accepted: November 6, 2023 Published: January 22, 2024
https://doi.org/10.18632/aging.205430How to Cite
Copyright: © 2024 Zhan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Alterations in autophagy are involved in pulmonary hypoxia/reoxygenation (H/R)-induced injury. Here, we intended to explain the function of microRNA-141-3p (miR-141-3p) in regulating autophagy under the H/R condition. Rat pulmonary microvascular endothelial cells (PMVECs) were applied for H/R cell model establishment, followed by tracing of autophagy formation. SIRT1 plays a critical role in controlling the lifespan of yeast, flies, and mice. Interaction between SIRT1 and Beclin-1, an indicator protein for autophagy, and between miR-141-3p and SIRT1 was assayed with their roles in PMVEC injury. Autophagy of PMVECs was activated after hypoxia treatment and further activated after H/R treatment. The binding of miR-141-3p and SIRT1 was verified. In H/R-treated PMVECs, the binding of miR-141-3p and SIRT1 was reduced. Furthermore, SIRT1 acted as a deacetylase to stabilize the Beclin-1 protein, promoting autophagy and PMVEC injury. H/R rat models were established, and in vivo, experiments further confirmed that miR-141-3p regulated autophagy and lung injury in H/R rats through SIRT1/Beclin-1 axis. The current study highlighted that reduced miR-141-3p in H/R-treated PMVECs promoted deacetylation of Beclin-1 by SIRT1, thus causing PMVEC injury.
Abbreviations
I/R: ischaemia-reperfusion; H/R: hypoxia and reoxygenation; PMVECs: pulmonary microvascular endothelial cells; miRNAs: microRNAs; SIRT1: sirtuin 1; SD: Sprague-Dawley; NC: negative control; oe: overexpression; H&E: hematoxylin and eosin; FBS: fetal bovine serum; RIPA: radioimmunoprecipitation assay; SDS-PAGE: sulphate-polyacrylamide gel electrophoresis; PVDF: polyvinylidene fluoride; HRP: horseradish peroxidase; RT-qPCR: reverse transcription-quantitative polymerase chain reaction; CCK-8: cell counting kit-8; IP: immunoprecipitation; RIP: RNA binding protein immunoprecipitation; ANOVA: analysis of variance.