Author: Vohwinkel, Christine U.; Coit, Ethan J.; Burns, Nana; Elajaili, Hanan; Hernandezâ€Saavedra, Daniel; Yuan, Xiaoyi; Eckle, Tobias; Nozik, Eva; Tuder, Rubin M.; Eltzschig, Holger K.
Title: Targeting alveolarâ€specific succinate dehydrogenase A attenuates pulmonary inflammation during acute lung injury Cord-id: z9suya1j Document date: 2021_3_9
ID: z9suya1j
Snippet: Acute lung injury (ALI) is an inflammatory lung disease, which manifests itself in patients as acute respiratory distress syndrome (ARDS). Previous studies have implicated alveolarâ€epithelial succinate in ALI protection. Therefore, we hypothesized that targeting alveolar succinate dehydrogenase SDH A would result in elevated succinate levels and concomitant lung protection. Wildâ€type (WT) mice or transgenic mice with targeted alveolarâ€epithelial Sdha or hypoxiaâ€inducible transcription fa
Document: Acute lung injury (ALI) is an inflammatory lung disease, which manifests itself in patients as acute respiratory distress syndrome (ARDS). Previous studies have implicated alveolarâ€epithelial succinate in ALI protection. Therefore, we hypothesized that targeting alveolar succinate dehydrogenase SDH A would result in elevated succinate levels and concomitant lung protection. Wildâ€type (WT) mice or transgenic mice with targeted alveolarâ€epithelial Sdha or hypoxiaâ€inducible transcription factor Hif1a deletion were exposed to ALI induced by mechanical ventilation. Succinate metabolism was assessed in alveolarâ€epithelial via mass spectrometry as well as redox measurements and evaluation of lung injury. In WT mice, ALI induced by mechanical ventilation decreased SDHA activity and increased succinate in alveolarâ€epithelial. In vitro, cellâ€permeable succinate decreased epithelial inflammation during stretch injury. Mice with inducible alveolarâ€epithelial Sdha deletion (Sdha(loxp/loxp) SPCâ€CreER mice) revealed reduced lung inflammation, improved alveolar barrier function, and attenuated histologic injury. Consistent with a functional role of succinate to stabilize HIF, Sdha(loxp/loxp) SPCâ€CreER experienced enhanced Hif1a levels during hypoxia or ALI. Conversely, Hif1a(loxp/loxp) SPCâ€CreER showed increased inflammation with ALI induced by mechanical ventilation. Finally, wildâ€type mice treated with intraâ€tracheal dimethlysuccinate were protected during ALI. These data suggest that targeting alveolarâ€epithelial SDHA dampens ALI via succinateâ€mediated stabilization of HIF1A. Translational extensions of our studies implicate succinate treatment in attenuating alveolar inflammation in patients suffering from ARDS.
Search related documents:
Co phrase search for related documents- acute ali lung injury and lung inflammation: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60
- acute ali lung injury and lung injury: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74
- acute ali lung injury and lung injury evaluation: 1
- acute ali lung injury and lung protection: 1, 2, 3, 4
- acute ards respiratory distress syndrome and lung disease: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73
- acute ards respiratory distress syndrome and lung inflammation: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72
- acute ards respiratory distress syndrome and lung injury: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75
- acute ards respiratory distress syndrome and lung injury evaluation: 1, 2
- acute ards respiratory distress syndrome and lung protection: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13
Co phrase search for related documents, hyperlinks ordered by date