Inhalation of an RNA aptamer that selectively binds extracellular histones protects from acute lung injury

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Autor(es): dc.contributorDuke University-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorVeterans Affairs Medical Center-
Autor(es): dc.contributorWave Life Sciences-
Autor(es): dc.contributorVeterans Affairs Tennessee Valley Healthcare-
Autor(es): dc.contributorVanderbilt University Medical Center-
Autor(es): dc.creatorLei, Beilei-
Autor(es): dc.creatorWang, Chaojian-
Autor(es): dc.creatorSnow, Kamie-
Autor(es): dc.creatorGraton, Murilo E.-
Autor(es): dc.creatorTighe, Robert M.-
Autor(es): dc.creatorFager, Ammon M.-
Autor(es): dc.creatorHoffman, Maureane R.-
Autor(es): dc.creatorGiangrande, Paloma H.-
Autor(es): dc.creatorMiller, Francis J.-
Data de aceite: dc.date.accessioned2025-08-21T19:41:03Z-
Data de disponibilização: dc.date.available2025-08-21T19:41:03Z-
Data de envio: dc.date.issued2023-07-29-
Data de envio: dc.date.issued2023-07-29-
Data de envio: dc.date.issued2023-03-14-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1016/j.omtn.2023.02.021-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/246940-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/246940-
Descrição: dc.descriptionAcute lung injury (ALI) is a syndrome of acute inflammation, barrier disruption, and hypoxemic respiratory failure associated with high morbidity and mortality. Diverse conditions lead to ALI, including inhalation of toxic substances, aspiration of gastric contents, infection, and trauma. A shared mechanism of acute lung injury is cellular toxicity from damage-associated molecular patterns (DAMPs), including extracellular histones. We recently described the selection and efficacy of a histone-binding RNA aptamer (HBA7). The current study aimed to identify the effects of extracellular histones in the lung and determine if HBA7 protected mice from ALI. Histone proteins decreased metabolic activity, induced apoptosis, promoted proinflammatory cytokine production, and caused endothelial dysfunction and platelet activation in vitro. HBA7 prevented these effects. The oropharyngeal aspiration of histone proteins increased neutrophil and albumin levels in bronchoalveolar lavage fluid (BALF) and precipitated neutrophil infiltration, interstitial edema, and barrier disruption in alveoli in mice. Similarly, inhaling wood smoke particulate matter, as a clinically relevant model, increased lung inflammation and alveolar permeability. Treatment by HBA7 alleviated lung injury in both models of ALI. These findings demonstrate the pulmonary delivery of HBA7 as a nucleic acid-based therapeutic for ALI.-
Descrição: dc.descriptionDefense Health Agency-
Descrição: dc.descriptionOffice of Research and Development-
Descrição: dc.descriptionU.S. Department of Veterans Affairs-
Descrição: dc.descriptionCongressionally Directed Medical Research Programs-
Descrição: dc.descriptionDepartment of Medicine Duke University-
Descrição: dc.descriptionSão Paulo State University School of Dentistry Campus of Aracatuba-
Descrição: dc.descriptionDepartment of Pathology Duke University-
Descrição: dc.descriptionVeterans Affairs Medical Center-
Descrição: dc.descriptionWave Life Sciences-
Descrição: dc.descriptionVeterans Affairs Tennessee Valley Healthcare-
Descrição: dc.descriptionDepartment of Medicine Vanderbilt University Medical Center-
Descrição: dc.descriptionSão Paulo State University School of Dentistry Campus of Aracatuba-
Descrição: dc.descriptionCongressionally Directed Medical Research Programs: W81XWH-16-1-0179-
Descrição: dc.descriptionCongressionally Directed Medical Research Programs: W81XWH-16-1-0180-
Formato: dc.format662-673-
Idioma: dc.languageen-
Relação: dc.relationMolecular Therapy - Nucleic Acids-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectendothelial cells-
Palavras-chave: dc.subjecthistones-
Palavras-chave: dc.subjectlung injury-
Palavras-chave: dc.subjectMT: Oligonucleotides: Therapies and Applications-
Palavras-chave: dc.subjectparticulate matter.-
Palavras-chave: dc.subjectRNA aptamer-
Palavras-chave: dc.subjectsmoke inhalation-
Título: dc.titleInhalation of an RNA aptamer that selectively binds extracellular histones protects from acute lung injury-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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