PloS one, 2015-09, Vol.10 (9), p.e0138625-e0138625
2015
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Details
- Autor(en) / Beteiligte
- Titel
- mTOR Overactivation and Compromised Autophagy in the Pathogenesis of Pulmonary Fibrosis
- Ist Teil von
- PloS one, 2015-09, Vol.10 (9), p.e0138625-e0138625
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2015
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The mammalian target of rapamycin (mTOR) signaling pathway in pulmonary fibrosis was investigated in cell and animal models. mTOR overactivation in alveolar epithelial cells (AECs) was achieved in the conditional and inducible Tsc1 knock-down mice SPC-rtTA/TetO-Cre/Tsc1(fx/+) (STT). Doxycycline caused Tsc1 knock-down and consequently mTOR activation in AECs for the STT mice. Mice treated with bleomycin exhibited increased mortality and pulmonary fibrosis compared with control mice. In wild-type C57BL/6J mice, pretreatment with rapamycin attenuated the bleomycin-mediated mortality and fibrosis. Rapamycin-mediated mouse survival benefit was inhibited by chloroquine, an autophagy inhibitor. Autophagosomes were decreased in the lungs after bleomycin exposure. Rapamycin induced the production of autophagosomes and diminished p62. We concluded that mTOR overactivation in AECs and compromised autophagy in the lungs are involved in the pathogenesis of pulmonary fibrosis. The suppression of mTOR and enhancement of autophagy may be used for treatment of pulmonary fibrosis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0138625Titel-ID: cdi_plos_journals_1719288623
- Format
- –
- Schlagworte
- Alveoli, Animal models, Animals, Autophagy, Autophagy (Cytology), Autophagy - physiology, Bleomycin, Care and treatment, Cell culture, Cell death, Chloroquine, Comparative analysis, Complications and side effects, Critical care, Development and progression, Disease, Disease Models, Animal, Doxycycline, Epithelial cells, Fibroblasts, Fibrosis, Health aspects, Hospitals, Humans, Kinases, Laboratories, Lung - metabolism, Lung - pathology, Lung diseases, Lungs, Medical prognosis, Medicine, Mice, Mice, Inbred C57BL, Mice, Transgenic, Molecular biology, Mortality, Pathogenesis, Pathology, Patient outcomes, Phagocytosis, Phagosomes, Physiology, Proteins, Pulmonary Alveoli - metabolism, Pulmonary Alveoli - pathology, Pulmonary fibrosis, Pulmonary Fibrosis - chemically induced, Pulmonary Fibrosis - metabolism, Pulmonary Fibrosis - pathology, Rapamycin, Respiratory tract diseases, Risk factors, Signal transduction, Signal Transduction - physiology, Thoracic surgery, TOR protein, TOR Serine-Threonine Kinases - genetics, TOR Serine-Threonine Kinases - metabolism, Transgenic animals, Tuberous Sclerosis Complex 1