Interplay between nuclear factor erythroid 2-related factor 2 and amphiregulin during mechanical ventilation.

Published on Oct 31, 2014in American Journal of Respiratory Cell and Molecular Biology6.914
路 DOI :10.1165/RCMB.2013-0279OC
Lucy Kathleen Reiss9
Estimated H-index: 9
,
Athanassios Fragoulis16
Estimated H-index: 16
+ 9 AuthorsChristoph Jan Wruck34
Estimated H-index: 34
Sources
Abstract
Mechanical ventilation (MV) elicits complex and clinically relevant cellular responses in the lungs. The current study was designed to define the role of the transcription factor nuclear factor erythroid 2鈥搑elated factor 2 (Nrf2), a major regulator of the cellular antioxidant defense system, in the pulmonary response to MV. Nrf2 activity was quantified in ventilated isolated perfused mouse lungs (IPL). Regulation of amphiregulin (AREG) was investigated in BEAS-2B cells with inactivated Nrf2 or Keap1, the inhibitor of Nrf2, using a luciferase vector with AREG promoter. AREG-dependent Nrf2 activity was examined in BEAS-2B cells, murine precision-cut lung slices (PCLS), and IPL. Finally, Nrf2 knockout and wild-type mice were ventilated to investigate the interplay between Nrf2 and AREG during MV in vivo. Lung functions and inflammatory parameters were measured. Nrf2 was activated in a ventilation-dependent manner. The knockdown of Nrf2 and Keap1 via short hairpin RNA in BEAS-2B cells and an EMSA with lung ti...
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