Details

Autor(en) / Beteiligte

• Bobba, Christopher M
• Fei, Qinqin
• Shukla, Vasudha
• Lee, Hyunwook
• Patel, Pragi
• Putman, Rachel K
• Spitzer, Carleen
• Tsai, MuChun
• Wewers, Mark D
• Lee, Robert J
• Christman, John W
• Ballinger, Megan N
• Ghadiali, Samir N
• Englert, Joshua A

Titel

Nanoparticle delivery of microRNA-146a regulates mechanotransduction in lung macrophages and mitigates injury during mechanical ventilation

Ist Teil von

• Nature communications, 2021-01, Vol.12 (1), p.289-13, Article 289

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• Mechanical ventilation generates injurious forces that exacerbate lung injury. These forces disrupt lung barrier integrity, trigger proinflammatory mediator release, and differentially regulate genes and non-coding oligonucleotides including microRNAs. In this study, we identify miR-146a as a mechanosensitive microRNA in alveolar macrophages that has therapeutic potential to mitigate lung injury during mechanical ventilation. We use humanized in-vitro systems, mouse models, and biospecimens from patients to elucidate the expression dynamics of miR-146a needed to decrease lung injury during mechanical ventilation. We find that the endogenous increase in miR-146a following injurious ventilation is not sufficient to prevent lung injury. However, when miR-146a is highly overexpressed using a nanoparticle delivery platform it is sufficient to prevent injury. These data indicate that the endogenous increase in microRNA-146a during mechanical ventilation is a compensatory response that partially limits injury and that nanoparticle delivery of miR-146a is an effective strategy for mitigating lung injury during mechanical ventilation.