Research ArticleAcute Lung Injury

Pazopanib ameliorates acute lung injuries via inhibition of MAP3K2 and MAP3K3

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Science Translational Medicine  28 Apr 2021:
Vol. 13, Issue 591, eabc2499
DOI: 10.1126/scitranslmed.abc2499

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ROS-mediated lung protection

Neutrophils accumulate in the lung after acute lung injury (ALI) where they play a role in the innate immune response through multiple mechanisms, including the production of reactive oxygen species (ROS). Here, Yuan et al. investigated the mechanisms regulating ROS production during ALI and developed a therapeutic intervention. The authors found that MAP3K2 and MAP3K3 inhibited ROS production from neutrophils. Pazopanib, a specific MAP3K2/3 inhibitor, ameliorated ALI in mice by modulating phosphorylation of p47, a subunit of Nox2. The treatment was effective in reducing pulmonary edema in a pilot study in patients who underwent lung transplantation, suggesting that targeting MAP3K2/3 might be effective for treating ALI of multiple etiologies.

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