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
View: Text | PDF
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

×

Figure 7

Cell signaling was disturbed in Ppl–/– mice.

Options: View larger image (or click on image) Download as PowerPoint
Cell signaling was disturbed in Ppl–/– mice. (A) Immunoblotting for STAT...
(A) Immunoblotting for STAT3 and P-STAT3 (Tyr705) was performed on Ppl+/+ and Ppl–/– lung homogenates at D0, D3, D7, and D14 after bleomycin instillation (n = 4). Histograms show a quantitative representation of P-STAT3/ STAT3 ratios. (B–I) P-STAT3 expression was assessed by immunostaining in lung sections from Ppl+/+ and Ppl–/– mice after bleomycin instillation. Figure is representative of at least 6 individual mice at each time. Magnification ×40. (J) Immunoblotting for STAT3 and P-STAT3 (Tyr705) was performed on CRISPR-Cas9 periplakin deleted (Ppl–/–) or WT (Ppl+/+) MLE-15 cells exposed to TGF-β1 for 24, 48, or 72 hours. The Western blot is representative for 3 different experiments. Quantitative evaluation of the Western blots for each time point is shown. (K) Immunoblotting for AKT and P-AKT (Ser473) was performed on Ppl+/+ and Ppl–/– lung homogenates on D0, D3, D7, and D14 after bleomycin instillation (n = 4). Histograms show a quantitative representation of P-Akt/Akt protein ratio.