Identification of periplakin as a major regulator of lung injury and repair in mice
Valérie Besnard, Rania Dagher, Tania Madjer, Audrey Joannes, Madeleine Jaillet, Martin Kolb, Philippe Bonniaud, Lynne A. Murray, Matthew A. Sleeman, Bruno Crestani
Valérie Besnard, Rania Dagher, Tania Madjer, Audrey Joannes, Madeleine Jaillet, Martin Kolb, Philippe Bonniaud, Lynne A. Murray, Matthew A. Sleeman, Bruno Crestani
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Research Article Inflammation Pulmonology

Identification of periplakin as a major regulator of lung injury and repair in mice

Abstract

Periplakin is a component of the desmosomes that acts as a cytolinker between intermediate filament scaffolding and the desmosomal plaque. Periplakin is strongly expressed by epithelial cells in the lung and is a target antigen for autoimmunity in idiopathic pulmonary fibrosis. The aim of this study was to determine the role of periplakin during lung injury and remodeling in a mouse model of lung fibrosis induced by bleomycin. We found that periplakin expression was downregulated in the whole lung and in alveolar epithelial cells following bleomycin-induced injury. Deletion of the Ppl gene in mice improved survival and reduced lung fibrosis development after bleomycin-induced injury. Notably, Ppl deletion promoted an antiinflammatory alveolar environment linked to profound changes in type 2 alveolar epithelial cells, including overexpression of antiinflammatory cytokines, decreased expression of profibrotic mediators, and altered cell signaling with a reduced response to TGF-β1. These results identify periplakin as a previously unidentified regulator of the response to injury in the lung.

Authors

Valérie Besnard, Rania Dagher, Tania Madjer, Audrey Joannes, Madeleine Jaillet, Martin Kolb, Philippe Bonniaud, Lynne A. Murray, Matthew A. Sleeman, Bruno Crestani

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Figure 6

αB-crystallin expression was decreased after Ppl deletion.

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αB-crystallin expression was decreased after Ppl deletion. (A) qPCR was ...
(A) qPCR was performed to estimate Cryab mRNA in whole-lung homogenate from Ppl+/+ and Ppl–/– lung homogenates after bleomycin instillation and normalized to B2m mRNA. Results are expressed as means ± SE of 5 animals per group. (B) αB-crystallin expression was assessed by immunostaining in lung sections from Ppl+/+ and Ppl–/– mice after bleomycin instillation. This figure is representative of at least 6 individual mice at each time point. Magnification ×40. (C) Cryab mRNA levels were estimated by qPCR in primary type 2 AECs from Ppl+/+ and Ppl–/– mice in control conditions and in response to either bleomycin or TGF-β1 and then normalized to B2m mRNA. Results are expressed as means ± SE of 5 animals per group; Mann Whitney U test.