Chao-Wei Ding, Jia-Yong Qiu, Hui Shen, Yi Yan, Ze-Xin Liu, Shen-Shen Huang, Yue-Jiao Ma, Zhi-Cheng Jing
Xiamen Humanity Hospital of Fujian Medical University. Second Hospital of Hebei Medical University. Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences and Southern Medical University. First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology. Affiliated Hospital of Yangzhou University and Yangzhou University. Shanghai Children’s Medical Center, National Children’s Medical Center and Shanghai Jiao Tong University School of Medicine.
China
Molecular Medicine
Mol Med 2026;
DOI: 10.1186/s10020-026-01478-5
Abstract
Pulmonary hypertension (PH) is a progressive, life-threatening cardiovascular disorder. It features irreversible pulmonary vascular remodeling and causes right ventricular failure and mortality. The underlying pathogenesis of PH is incompletely elucidated. Ubiquitination is a reversible post-translational modification. It regulates protein degradation and membrane trafficking and contributes critically to PH development and progression. The ubiquitin-proteasome system (UPS), especially E3 ubiquitin ligases and Deubiquitinases, modulates the function of pulmonary artery endothelial cells and pulmonary artery
smooth muscle cells in PH. These molecules exert distinct roles and regulatory mechanisms in PH-related signaling pathways. The pathways include bone morphogenetic protein, nuclear factor kappa B (NF-κB), hypoxia inducible factor-1α, P53, Hippo, and mitochondrial quality control. UPS-targeted small-molecule agents, proteasome inhibitors, and proteolysis-targeting chimeras have therapeutic potential for PH. They also face notable translational challenges. Ubiquitination provides new
mechanistic insights into PH pathogenesis and identifies innovative avenues for targeted therapy.
Category
Vascular Cell Biology and Mechanisms of Pulmonary Vascular Disease
Review Articles Concerning Pulmonary Vascular Disease
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes