Research Paper Volume 12, Issue 7 pp 5716—5732
Ube2s-stabilized β-catenin protects against myocardial ischemia/reperfusion injury by activating HIF-1α signaling
- 1 Department of Pharmacy, The Second Affiliated Hospital of Air Force Medical University, Xi’an, China
- 2 Department of Cardiology, The Second Affiliated Hospital of Air Force Medical University, Xi’an, China
received: June 28, 2019 ; accepted: February 22, 2020 ; published: April 6, 2020 ;https://doi.org/10.18632/aging.102960
How to Cite
Copyright © 2020 Chen 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.
The activation of hypoxia-inducible factor (HIF) is an important event for mediating the adaptive response to myocardial ischemia/reperfusion (MI/R) injury. The ubiquitin-conjugating enzyme E2S (Ube2s) catalyzes ubiquitin conjugation to target proteins. Here, we report the positive regulation of HIF-1α signaling by Ube2s via stabilizing β-catenin, by which Ube2s acts to protect against MI/R injury. We show that Ube2s expression is upregulated in the hearts of mice subjected to MI/R injury. Functionally, Ube2s depletion exacerbates and its overexpression ameliorates MI/R injury. In addition, Ube2s augments the activation of HIF-1α and reduces myocardial apoptosis. Moreover, Ube2s induces the accumulation of β-Catenin through increasing its stabilization. Importantly, β-Catenin knockdown abrogates Ube2s-augmented HIF-1α activation, and meanwhile, diminishes the protective effect of Ube2s on MI/R injury, thus establishing a causal link between Ube2s-stabilized β-catenin and HIF-1α-mediated myocardial protection. Altogether, this study identifies the Ube2s/β-catenin/HIF-1α axis as a novel protective regulator involved in MI/R injury, and also implies that it might represent a potential therapeutic target for ameliorating MI/R injury.