Targeting p16INK4a reverses alveolar epithelial cell dysfunction and induces lung regeneration in emphysema
Ribeiro Baptista, B.; Toigo, M.; Justeau, G.; Abou-atmeh, P.; De Freitas Castro, T.; Zysman, M.; Thiebaut De Menonville, C.; Audureau, E.; Schnyder, K.; Wang, H.; Hu, Y.; Koenigshoff, M.; Lanone, S.; Chabot, F.; Zana-Taieb, E.; Jourdan Le Saux, C.; Lehmann, M.; Derumeaux, G.; Boczkowski, J.; Gote-Schniering, J.; Boyer, L.
Show abstract
Pulmonary emphysema involves impaired regenerative capacity of alveolar type 2 epithelial cells (AT2), the main progenitor cells in alveoli. However, the mechanisms underlying dysfunctional epithelial repair remain unclear. In a mouse model of elastase-induced emphysema, we observed an accumulation of activated AT2s in the lung, associated with an overexpression of p16INK4a (p16), a cell cycle inhibitor known to influence stem cell fate. Deletion of p16 promoted the transition of AT2 into alveolar type 1 (AT1) cells, resulting in tissue regeneration in both mice and alveolar organoids. Pharmacological targeting of the p16 pathway using senolytic agents recapitulate this regenerative effect, further supporting the role of p16 as a key brake on epithelial plasticity. These findings demonstrate that alveolar epithelial cell dysfunction can be reversed by p16 deletion or by eliminating p16+ cells, thereby reactivating the AT2-to-AT1 transition and promoting endogenous alveolar regeneration. This work identifies the p16 pathway as a promising therapeutic target for restoring damaged alveoli in emphysema.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Hypoxia promotes airway differentiation in the human lung epithelium 96%
- Generation of human alveolar epithelial type I cells from pluripotent stem cells 95%
- SARS-CoV-2 Infection of Pluripotent Stem Cell-derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response 95%
Similar papers in this journal
- A Unique Cellular Organization of Human Distal Airways and Its Disarray in Chronic Obstructive Pulmonary Disease 97%
- Prenatal VEGF Nano-Delivery Reverses Congenital Diaphragmatic Hernia-Associated Pulmonary Abnormalities 95%
- Endogenous Retroviral Elements Generate Pathologic Neutrophils and Elastase Rich Exosomes in Pulmonary Arterial Hypertension 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.