Yap/Taz regulate alveolar regeneration and resolution of lung inflammation
| Autor: | Ying Tian, Peggy Zhang, Marla R. Wolfson, Harold A. Chapman, Beata Kosmider, Edward E. Morrisey, Lauren Tragesser, Yan Wang, Daniela Liccardo, Walter J. Koch, Ryan LaCanna, Tongtong Cao, Hao Shen |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Pulmonology Cell Cycle Proteins Stem cells Inbred C57BL Regenerative Medicine Medical and Health Sciences Epithelium Transgenic Mice 0302 clinical medicine Bacterial infections 2.1 Biological and endogenous factors Aetiology Lung Adult stem cells Stem Cells NF-kappa B Adaptor Proteins Cell Differentiation General Medicine respiratory system Pulmonary Surfactant-Associated Protein C Cell biology Streptococcus pneumoniae Infectious Diseases medicine.anatomical_structure 030220 oncology & carcinogenesis Pneumonia & Influenza Respiratory Pneumococcal Stem Cell Research - Nonembryonic - Non-Human medicine.symptom Stem cell Infection Research Article Signal Transduction Biotechnology Alveolar Epithelium Immunology Mice Transgenic Inflammation 03 medical and health sciences Rare Diseases Downregulation and upregulation medicine Animals Humans Regeneration Adaptor Proteins Signal Transducing Cell Proliferation Cell Nucleus Hippo signaling pathway business.industry Regeneration (biology) Signal Transducing Epithelial Cells YAP-Signaling Proteins Pneumonia Pneumonia Pneumococcal Stem Cell Research medicine.disease respiratory tract diseases Mice Inbred C57BL HEK293 Cells 030104 developmental biology Alveolar Epithelial Cells Trans-Activators business |
| Zdroj: | The Journal of clinical investigation, vol 129, iss 5 |
| ISSN: | 1558-8238 0021-9738 |
| DOI: | 10.1172/jci125014 |
| Popis: | Alveolar epithelium plays a pivotal role in protecting the lungs from inhaled infectious agents. Therefore, the regenerative capacity of the alveolar epithelium is critical for recovery from these insults in order to rebuild the epithelial barrier and restore pulmonary functions. Here, we show that sublethal infection of mice with Streptococcus pneumoniae, the most common pathogen of community-acquired pneumonia, led to exclusive damage in lung alveoli, followed by alveolar epithelial regeneration and resolution of lung inflammation. We show that surfactant protein C–expressing (SPC-expressing) alveolar epithelial type II cells (AECIIs) underwent proliferation and differentiation after infection, which contributed to the newly formed alveolar epithelium. This increase in AECII activities was correlated with increased nuclear expression of Yap and Taz, the mediators of the Hippo pathway. Mice that lacked Yap/Taz in AECIIs exhibited prolonged inflammatory responses in the lung and were delayed in alveolar epithelial regeneration during bacterial pneumonia. This impaired alveolar epithelial regeneration was paralleled by a failure to upregulate IκBa, the molecule that terminates NF-κB–mediated inflammatory responses. These results demonstrate that signals governing resolution of lung inflammation were altered in Yap/Taz mutant mice, which prevented the development of a proper regenerative niche, delaying repair and regeneration of alveolar epithelium during bacterial pneumonia. |
| Databáze: | OpenAIRE |
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