ArticleAmerican journal of physiology. Lung cellular and molecular physiology2023
Ultrasound-guided transfection of claudin-5 improves lung endothelial barrier function in lung injury without impairing innate immunity.
Article in American journal of physiology. Lung cellular and molecular physiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 8 citations in OpenAlex.
- Measuring and managing pulmonary edema in ARDS: a narrative review.Critical care (London, England) · 2026Review
- Low-pressure exposure influences the development of HAPE.Open life sciences · 2025Article
- Calcitriol Administration Attenuates Acute Lung Injury by Improving Angiopoietin/Tie2 Dysregulation and Alveolar-Capillary Barrier Integrity in a Mouse Model of Ovariectomy Complicated With Sepsis.Mediators of inflammation · 2025Article
- Alternative Strategies for Delivering Immunotherapeutics Targeting the PD-1/PD-L1 Immune Checkpoint in Cancer.Pharmaceutics · 2024Review
- Secretome profiling of human epithelial cells exposed to cigarette smoke extract and their effect on human lung microvascular endothelial cells.Scientific reports · 2024Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
In acute lung injury, the lung endothelial barrier is compromised. Loss of endothelial barrier integrity occurs in association with decreased levels of the tight junction protein claudin-5. Restoration of their levels by gene transfection may improve the vascular barrier, but how to limit transfection solely to regions of the lung that are injured is unknown. We hypothesized that thoracic ultrasound in combination with intravenous microbubbles (USMBs) could be used to achieve regional gene transfection in injured lung regions and improve endothelial barrier function. Since air blocks ultrasound energy, insonation of the lung is only achieved in areas of lung injury (edema and atelectasis); healthy lung is spared. Cavitation of the microbubbles achieves local tissue transfection. Here we demonstrate successful USMB-mediated gene transfection in the injured lungs of mice. After thoracic insonation, transfection was confined to the lung and only occurred in the setting of injured (but not healthy) lung. In a mouse model of acute lung injury, we observed downregulation of endogenous claudin-5 and an acute improvement in lung vascular leakage and in oxygenation after claudin-5 overexpression by transfection. The improvement occurred without any impairment of the immune response as measured by pathogen clearance, alveolar cytokines, and lung histology. In conclusion, USMB-mediated transfection targets injured lung regions and is a novel approach to the treatment of lung injury.
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