The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2022
Venovenous extracorporeal membrane oxygenation promotes alveolar epithelial recovery by activating Hippo/YAP signaling after lung injury.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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Huang Jian, Zhang Rongzhi, Zhai Kerong, Li Jian, Yao Min, Wei Shilin, Cheng Xingdong, Yang Jianbao, Gao Bingren, Wu Xiangyang, Li Yongnan
Аннотация
BACKGROUND: The preferred configuration for bridging patients with respiratory failure while awaiting lung transplantation is venovenous extracorporeal membrane oxygenation (VV ECMO). However, the protective effect of VV ECMO on the lung, as well as the underlying mechanisms, are still unknown.
METHODS: We investigated the role of VV ECMO in preventing lung injury in vivo using a rat model. Additionally, the effects of Hippo/YAP signaling on alveolar epithelial type II cells (AT2)-mediated alveolar epithelial recovery in VV ECMO rats were also investigated. In the bronchoalveolar lavage fluid (BALF) and lung tissue, RNA sequencing, lung injury, edema, and cytokine expression were evaluated.
RESULTS: VV ECMO significantly improved severe hypoxemia, reduced lung edema, and inflammatory response, and altered alveolar epithelial function, as indicated by reduced protein concentrations in BALF. This was associated with Hippo/YAP signaling activation, according to RNA sequencing analysis. Furthermore, we discovered that after VV ECMO, AT2 cells proliferated and differentiated, and this increase in AT2 cell activity was correlated to the increased nuclear expression of YAP, which is critical for alveolar epithelial recovery from lung injury. During VV ECMO, verteporfin-induced YAP inhibition and the loss of the oxygenator delayed lung alveolar epithelial recovery and led to a prolonged inflammatory response.
CONCLUSIONS: These findings suggest that VV ECMO protects against lung injury by activating the Hippo/YAP signaling pathway. Strategies aimed at increasing YAP activity in AT2 cells could thus aid alveolar epithelial recovery, making VV ECMO easier for lung transplantation.
METHODS: We investigated the role of VV ECMO in preventing lung injury in vivo using a rat model. Additionally, the effects of Hippo/YAP signaling on alveolar epithelial type II cells (AT2)-mediated alveolar epithelial recovery in VV ECMO rats were also investigated. In the bronchoalveolar lavage fluid (BALF) and lung tissue, RNA sequencing, lung injury, edema, and cytokine expression were evaluated.
RESULTS: VV ECMO significantly improved severe hypoxemia, reduced lung edema, and inflammatory response, and altered alveolar epithelial function, as indicated by reduced protein concentrations in BALF. This was associated with Hippo/YAP signaling activation, according to RNA sequencing analysis. Furthermore, we discovered that after VV ECMO, AT2 cells proliferated and differentiated, and this increase in AT2 cell activity was correlated to the increased nuclear expression of YAP, which is critical for alveolar epithelial recovery from lung injury. During VV ECMO, verteporfin-induced YAP inhibition and the loss of the oxygenator delayed lung alveolar epithelial recovery and led to a prolonged inflammatory response.
CONCLUSIONS: These findings suggest that VV ECMO protects against lung injury by activating the Hippo/YAP signaling pathway. Strategies aimed at increasing YAP activity in AT2 cells could thus aid alveolar epithelial recovery, making VV ECMO easier for lung transplantation.