ATF3 Protects Pulmonary Resident Cells from Acute and Ventilator-Induced Lung Injury by Preventing Nrf2 Degradation

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ATF3 Protects Pulmonary Resident Cells from Acute and Ventilator-Induced Lung Injury by Preventing Nrf2 Degradation. / Shan, Yuexin; Akram, Ali; Amatullah, Hajera; Zhou, Dun Yuan; Gali, Patricia L.; Maron-Gutierrez, Tatiana; Gonzalez-Lopez, Adrian; Zhou, Louis; Rocco, Patricia R. M.; Hwang, David; Albaiceta, Guillermo M.; Haitsma, Jack J.; dos Santos, Claudia C.

I: Antioxidants & Redox Signaling, Vol. 22, Nr. 8, 2015, s. 651-668.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Shan, Y, Akram, A, Amatullah, H, Zhou, DY, Gali, PL, Maron-Gutierrez, T, Gonzalez-Lopez, A, Zhou, L, Rocco, PRM, Hwang, D, Albaiceta, GM, Haitsma, JJ & dos Santos, CC 2015, 'ATF3 Protects Pulmonary Resident Cells from Acute and Ventilator-Induced Lung Injury by Preventing Nrf2 Degradation', Antioxidants & Redox Signaling, vol. 22, nr. 8, s. 651-668. https://doi.org/10.1089/ars.2014.5987

APA

Shan, Y., Akram, A., Amatullah, H., Zhou, D. Y., Gali, P. L., Maron-Gutierrez, T., Gonzalez-Lopez, A., Zhou, L., Rocco, P. R. M., Hwang, D., Albaiceta, G. M., Haitsma, J. J., & dos Santos, C. C. (2015). ATF3 Protects Pulmonary Resident Cells from Acute and Ventilator-Induced Lung Injury by Preventing Nrf2 Degradation. Antioxidants & Redox Signaling, 22(8), 651-668. https://doi.org/10.1089/ars.2014.5987

CBE

Shan Y, Akram A, Amatullah H, Zhou DY, Gali PL, Maron-Gutierrez T, Gonzalez-Lopez A, Zhou L, Rocco PRM, Hwang D, Albaiceta GM, Haitsma JJ, dos Santos CC. 2015. ATF3 Protects Pulmonary Resident Cells from Acute and Ventilator-Induced Lung Injury by Preventing Nrf2 Degradation. Antioxidants & Redox Signaling. 22(8):651-668. https://doi.org/10.1089/ars.2014.5987

MLA

Vancouver

Author

Shan, Yuexin ; Akram, Ali ; Amatullah, Hajera ; Zhou, Dun Yuan ; Gali, Patricia L. ; Maron-Gutierrez, Tatiana ; Gonzalez-Lopez, Adrian ; Zhou, Louis ; Rocco, Patricia R. M. ; Hwang, David ; Albaiceta, Guillermo M. ; Haitsma, Jack J. ; dos Santos, Claudia C. / ATF3 Protects Pulmonary Resident Cells from Acute and Ventilator-Induced Lung Injury by Preventing Nrf2 Degradation. I: Antioxidants & Redox Signaling. 2015 ; Vol. 22, Nr. 8. s. 651-668.

RIS

TY - JOUR

T1 - ATF3 Protects Pulmonary Resident Cells from Acute and Ventilator-Induced Lung Injury by Preventing Nrf2 Degradation

AU - Shan, Yuexin

AU - Akram, Ali

AU - Amatullah, Hajera

AU - Zhou, Dun Yuan

AU - Gali, Patricia L.

AU - Maron-Gutierrez, Tatiana

AU - Gonzalez-Lopez, Adrian

AU - Zhou, Louis

AU - Rocco, Patricia R. M.

AU - Hwang, David

AU - Albaiceta, Guillermo M.

AU - Haitsma, Jack J.

AU - dos Santos, Claudia C.

PY - 2015

Y1 - 2015

N2 - Aims: Ventilator-induced lung injury (VILI) contributes to mortality in patients with acute respiratory distress syndrome, the most severe form of acute lung injury (ALI). Absence of activating transcription factor 3 (ATF3) confers susceptibility to ALI/VILI. To identify cell-specific ATF3-dependent mechanisms of susceptibility to ALI/VILI, we generated ATF3 chimera by adoptive bone marrow (BM) transfer and randomized to inhaled saline or lipopolysacharide (LPS) in the presence of mechanical ventilation (MV). Adenovirus vectors to silence or overexpress ATF3 were used in primary human bronchial epithelial cells and murine BM-derived macrophages from wild-type or ATF3-deficient mice. Results: Absence of ATF3 in myeloid-derived cells caused increased pulmonary cellular infiltration. In contrast, absence of ATF3 in parenchymal cells resulted in loss of alveolar-capillary membrane integrity and increased exudative edema. ATF3-deficient macrophages were unable to limit the expression of pro-inflammatory mediators. Knockdown of ATF3 in resident cells resulted in decreased junctional protein expression and increased paracellular leak. ATF3 overexpression abrogated LPS induced membrane permeability. Despite release of ATF3-dependent Nrf2 transcriptional inhibition, mice that lacked ATF3 expression in resident cells had increased Nrf2 protein degradation. Innovation: In our model, in the absence of ATF3 in parenchymal cells increased Nrf2 degradation is the result of increased Keap-1 expression and loss of DJ-1 (Parkinson disease [autosomal recessive, early onset] 7), previously not known to play a role in lung injury. Conclusion: Results suggest that ATF3 confers protection to lung injury by preventing inflammatory cell recruitment and barrier disruption in a cell-specific manner, opening novel opportunities for cell specific therapy for ALI/VILI. Antioxid. Redox Signal. 22, 651-668.

AB - Aims: Ventilator-induced lung injury (VILI) contributes to mortality in patients with acute respiratory distress syndrome, the most severe form of acute lung injury (ALI). Absence of activating transcription factor 3 (ATF3) confers susceptibility to ALI/VILI. To identify cell-specific ATF3-dependent mechanisms of susceptibility to ALI/VILI, we generated ATF3 chimera by adoptive bone marrow (BM) transfer and randomized to inhaled saline or lipopolysacharide (LPS) in the presence of mechanical ventilation (MV). Adenovirus vectors to silence or overexpress ATF3 were used in primary human bronchial epithelial cells and murine BM-derived macrophages from wild-type or ATF3-deficient mice. Results: Absence of ATF3 in myeloid-derived cells caused increased pulmonary cellular infiltration. In contrast, absence of ATF3 in parenchymal cells resulted in loss of alveolar-capillary membrane integrity and increased exudative edema. ATF3-deficient macrophages were unable to limit the expression of pro-inflammatory mediators. Knockdown of ATF3 in resident cells resulted in decreased junctional protein expression and increased paracellular leak. ATF3 overexpression abrogated LPS induced membrane permeability. Despite release of ATF3-dependent Nrf2 transcriptional inhibition, mice that lacked ATF3 expression in resident cells had increased Nrf2 protein degradation. Innovation: In our model, in the absence of ATF3 in parenchymal cells increased Nrf2 degradation is the result of increased Keap-1 expression and loss of DJ-1 (Parkinson disease [autosomal recessive, early onset] 7), previously not known to play a role in lung injury. Conclusion: Results suggest that ATF3 confers protection to lung injury by preventing inflammatory cell recruitment and barrier disruption in a cell-specific manner, opening novel opportunities for cell specific therapy for ALI/VILI. Antioxid. Redox Signal. 22, 651-668.

U2 - 10.1089/ars.2014.5987

DO - 10.1089/ars.2014.5987

M3 - Article

C2 - 25401197

VL - 22

SP - 651

EP - 668

JO - Antioxidants and Redox Signaling

JF - Antioxidants and Redox Signaling

SN - 1557-7716

IS - 8

ER -