Lung inflammation and interstitial fibrosis by targeted alveolar epithelial type I cell death - 20/03/24
Resumen |
Introduction |
The pathogenesis of chronic lung diseases is multifaceted with a major role of recurrent micro-injuries of the epithelium. While several reports clearly indicated a prominent role for surfactant-producing alveolar epithelial type 2 (AT2) cells, the contribution of gas exchange permissive alveolar epithelial type 1 (AT1) cells has not been addressed yet. Here, we investigated whether repeated injury of AT1 cells leads to inflammation and interstitial fibrosis.
Methods |
We chose an inducible model of AT1 cell depletion following local diphtheria toxin (DT) administration using an iDTRfl/fl X Aquaporin 5CRE (Aqp5CRE) transgenic mouse strain.
Results |
We investigated repeated doses and intervals of DT to induce cell death of AT1 cells causing inflammation and interstitial fibrosis. We found that repeated DT administrations of 1ng DT in iDTRfl/fl X Aquaporin 5CRE mice causes AT1 cell death leading to inflammation, increased tissue repair markers and interstitial pulmonary fibrosis.
Conclusion |
Together, we demonstrate that depletion of AT1 cells using repeated injury represents a novel approach to investigate chronic lung inflammatory diseases and to identify new therapeutic targets.
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Vol 41 - N° 3
P. 221 - mars 2024 Regresar al número¿Ya suscrito a @@106933@@ revista ?