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Poly(ADP-ribose) polymerase-1 (PARP-1) controls lung cell proliferation and repair after hyperoxia-induced lung damage

Abstract : Oxygen-based therapies expose lung to elevated levels of ROS and induce lung cell damage and inflammation. Injured cells are replaced through increased proliferation and differentiation of epithelial cells and fibroblasts. Failure to modulate these processes leads to excessive cell proliferation, collagen deposition, fibrosis, and chronic lung disease. Poly(ADP-ribose) polymerase-1 (PARP-1) is activated in response to DNA damage and participates in DNA repair, genomic integrity, and cell death. In this study, we evaluated the role of PARP-1 in lung repair during recovery after acute hyperoxia exposure. We exposed PARP-1 -/- and wild-type mice for 64 h to 100% hyperoxia and let them recover in air for 5-21 days. PARP-1-deficient mice exhibited significantly higher lung cell hyperplasia and proliferation than PARP-1 +/+ animals after 5 and 10 days of recovery. This was accompanied by an increased inflammatory response in PARP-1 -/- compared with wild-type animals, characterized by neutrophil infiltration and increased IL-6 levels in bronchoalveolar lavages. These lesions were reversible, since the extent of the hyperplastic regions was reduced after 21 days of recovery and did not result in fibrosis. In vitro, lung primary fibroblasts derived from PARP-1 -/- mice showed a higher proliferative response than PARP-1 +/+ cells during air recovery after hyperoxia-induced growth arrest. Altogether, these results reveal an essential role of PARP-1 in the control of cell repair and tissue remodeling after hyperoxia-induced lung injury.
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Contributor : Ludovic Leloup Connect in order to contact the contributor
Submitted on : Wednesday, May 23, 2018 - 10:56:35 AM
Last modification on : Thursday, October 21, 2021 - 3:58:37 AM




Alessandra Pagano, Isabelle Métrailler-Ruchonnet, Michel Aurrand-Lions, Monica Lucattelli, Yves Donati, et al.. Poly(ADP-ribose) polymerase-1 (PARP-1) controls lung cell proliferation and repair after hyperoxia-induced lung damage. American Journal of Physiology - Lung Cellular and Molecular Physiology, 2007, 293 (3), pp.L619 - L629. ⟨10.1152/ajplung.00037.2007⟩. ⟨hal-01798135⟩



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