ArticleAmerican journal of physiology. Lung cellular and molecular physiology2021
UCHL1, a deubiquitinating enzyme, regulates lung endothelial cell permeability in vitro and in vivo.
Article in American journal of physiology. Lung cellular and molecular physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Deubiquitinases as Regulators and Therapeutic Targets in Vascular Diseases.International journal of molecular sciences · 2026Review
- Prognostic genes in hepatocellular carcinoma and their function: an analysis integrating high-throughput-based spatial transcriptomics and single-cell RNA-sequencing.Journal of gastrointestinal oncology · 2026Article
- Defining the Systemic Response to Flight After Polytrauma in a Murine Model.Military medicine · 2026Article
- Article
- Nanomechanical Characterization of E-Cigarette-Induced Lung Endothelial Dysfunction: Roles of Cortactin and Mitochondrial Reactive Oxygen Species.International journal of molecular sciences · 2025Article
- Acute lung injury induced by traumatic hemorrhagic shock: pathogenesis, biomarkers and therapeutic perspectives.World journal of emergency medicine · 2025Article
- Ubiquitin-proteasome system: a potential participant and therapeutic target in antiphospholipid syndrome.Frontiers in immunology · 2025Review
- Deubiquitinase UCHL1 promotes angiogenesis and blood-spinal cord barrier function recovery after spinal cord injury by stabilizing Sox17.Cellular and molecular life sciences : CMLS · 2024Article
- Article
- Pathophysiology and pathogenic mechanisms of pulmonary hypertension: role of membrane receptors, ion channels, and CaPhysiological reviews · 2023Review
- eNAMPT neutralization reduces preclinical ARDS severity via rectified NFkB and Akt/mTORC2 signaling.Scientific reports · 2022Article
- UCHL1 as a novel target in breast cancer: emerging insights from cell and chemical biology.British journal of cancer · 2022Review
- Loss of SOX18/CLAUDIN5 disrupts the pulmonary endothelial barrier in ventilator-induced lung injury.Frontiers in physiology · 2022Article
- Integrin Beta 4E Promotes Endothelial Phenotypic Changes and Attenuates Lung Endothelial Cell Inflammatory Responses.Frontiers in physiology · 2022Article
- Mechanisms of Mechanical Force Induced Pulmonary Vascular Endothelial Hyperpermeability.Frontiers in physiology · 2021Review
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Increasing evidence suggests an important role for deubiquitinating enzymes (DUBs) in modulating a variety of biological functions and diseases. We previously identified the upregulation of the DUB ubiquitin carboxyl terminal hydrolase 1 (UCHL1) in murine ventilator-induced lung injury (VILI). However, the role of UCHL1 in modulating vascular permeability, a cardinal feature of acute lung injury (ALI) in general, remains unclear. We investigated the role of UCHL1 in pulmonary endothelial cell (EC) barrier function in vitro and in vivo and examined the effects of UCHL1 on VE-cadherin and claudin-5 regulation, important adherens and tight junctional components, respectively. Measurements of transendothelial electrical resistance confirmed decreased barrier enhancement induced by hepatocyte growth factor (HGF) and increased thrombin-induced permeability in both UCHL1-silenced ECs and in ECs pretreated with LDN-57444 (LDN), a pharmacological UCHL1 inhibitor. In addition, UCHL1 knockdown (siRNA) was associated with decreased expression of VE-cadherin and claudin-5, whereas silencing of the transcription factor FoxO1 restored claudin-5 levels. Finally, UCHL1 inhibition in vivo via LDN was associated with increased VILI in a murine model. These findings support a prominent functional role of UCHL1 in regulating lung vascular permeability via alterations in adherens and tight junctions and implicate UCHL1 as an important mediator of ALI.
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