mTOR Overactivation and Compromised Autophagy in the Pathogenesis of Pulmonary Fibrosis.
Identifieur interne : 000E64 ( Main/Exploration ); précédent : 000E63; suivant : 000E65mTOR Overactivation and Compromised Autophagy in the Pathogenesis of Pulmonary Fibrosis.
Auteurs : Yao-Song Gui [République populaire de Chine] ; Lianmei Wang [République populaire de Chine] ; Xinlun Tian [République populaire de Chine] ; Xue Li [République populaire de Chine] ; Aiping Ma [République populaire de Chine] ; Weixun Zhou [République populaire de Chine] ; Ni Zeng [République populaire de Chine] ; Ji Zhang [République populaire de Chine] ; Baiqiang Cai [République populaire de Chine] ; Hongbing Zhang [République populaire de Chine] ; Jing-Yu Chen [République populaire de Chine] ; Kai-Feng Xu [République populaire de Chine]Source :
- PloS one [ 1932-6203 ] ; 2015.
Descripteurs français
- KwdFr :
- Alvéoles pulmonaires (anatomopathologie), Alvéoles pulmonaires (métabolisme), Animaux, Autophagie (physiologie), Bléomycine, Fibrose pulmonaire (), Fibrose pulmonaire (anatomopathologie), Fibrose pulmonaire (métabolisme), Humains, Modèles animaux de maladie humaine, Poumon (anatomopathologie), Poumon (métabolisme), Souris, Souris de lignée C57BL, Souris transgéniques, Sérine-thréonine kinases TOR (génétique), Sérine-thréonine kinases TOR (métabolisme), Transduction du signal (physiologie).
- MESH :
- anatomopathologie : Alvéoles pulmonaires, Fibrose pulmonaire, Poumon.
- génétique : Sérine-thréonine kinases TOR.
- métabolisme : Alvéoles pulmonaires, Fibrose pulmonaire, Poumon, Sérine-thréonine kinases TOR.
- physiologie : Autophagie, Transduction du signal.
- Animaux, Bléomycine, Fibrose pulmonaire, Humains, Modèles animaux de maladie humaine, Souris, Souris de lignée C57BL, Souris transgéniques.
English descriptors
- KwdEn :
- Animals, Autophagy (physiology), Bleomycin, Disease Models, Animal, Humans, Lung (metabolism), Lung (pathology), Mice, Mice, Inbred C57BL, Mice, Transgenic, Pulmonary Alveoli (metabolism), Pulmonary Alveoli (pathology), Pulmonary Fibrosis (chemically induced), Pulmonary Fibrosis (metabolism), Pulmonary Fibrosis (pathology), Signal Transduction (physiology), TOR Serine-Threonine Kinases (genetics), TOR Serine-Threonine Kinases (metabolism).
- MESH :
- chemical , genetics : TOR Serine-Threonine Kinases.
- chemical , metabolism : TOR Serine-Threonine Kinases.
- chemical : Bleomycin.
- chemically induced : Pulmonary Fibrosis.
- metabolism : Lung, Pulmonary Alveoli, Pulmonary Fibrosis.
- pathology : Lung, Pulmonary Alveoli, Pulmonary Fibrosis.
- physiology : Autophagy, Signal Transduction.
- Animals, Disease Models, Animal, Humans, Mice, Mice, Inbred C57BL, Mice, Transgenic.
Abstract
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.
DOI: 10.1371/journal.pone.0138625
PubMed: 26382847
Affiliations:
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Le document en format XML
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China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Respiratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Wang, Lianmei" sort="Wang, Lianmei" uniqKey="Wang L" first="Lianmei" last="Wang">Lianmei Wang</name><affiliation wicri:level="3"><nlm:affiliation>State Key Laboratory of Medical Molecular Biology, Department of Physiology and Pathophysiology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Medical Molecular Biology, 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type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Li, Xue" sort="Li, Xue" uniqKey="Li X" first="Xue" last="Li">Xue Li</name><affiliation wicri:level="3"><nlm:affiliation>Department of Respiratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Respiratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Ma, Aiping" sort="Ma, Aiping" uniqKey="Ma A" first="Aiping" last="Ma">Aiping Ma</name><affiliation wicri:level="3"><nlm:affiliation>Department of Respiratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Respiratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Zhou, Weixun" sort="Zhou, Weixun" uniqKey="Zhou W" first="Weixun" last="Zhou">Weixun Zhou</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Zeng, Ni" sort="Zeng, Ni" uniqKey="Zeng N" first="Ni" last="Zeng">Ni Zeng</name><affiliation wicri:level="3"><nlm:affiliation>Department of Respiratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Respiratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Zhang, Ji" sort="Zhang, Ji" uniqKey="Zhang J" first="Ji" last="Zhang">Ji Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Thoracic Surgery, Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery, Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi</wicri:regionArea><wicri:noRegion>Wuxi</wicri:noRegion></affiliation></author><author><name sortKey="Cai, Baiqiang" sort="Cai, Baiqiang" uniqKey="Cai B" first="Baiqiang" last="Cai">Baiqiang Cai</name><affiliation wicri:level="3"><nlm:affiliation>Department of Respiratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Respiratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Zhang, Hongbing" sort="Zhang, Hongbing" uniqKey="Zhang H" first="Hongbing" last="Zhang">Hongbing Zhang</name><affiliation wicri:level="3"><nlm:affiliation>State Key Laboratory of Medical Molecular Biology, Department of Physiology and Pathophysiology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Medical Molecular Biology, Department of Physiology and Pathophysiology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Chen, Jing Yu" sort="Chen, Jing Yu" uniqKey="Chen J" first="Jing-Yu" last="Chen">Jing-Yu Chen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Thoracic Surgery, Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Thoracic Surgery, Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi</wicri:regionArea><wicri:noRegion>Wuxi</wicri:noRegion></affiliation></author><author><name sortKey="Xu, Kai Feng" sort="Xu, Kai Feng" uniqKey="Xu K" first="Kai-Feng" last="Xu">Kai-Feng Xu</name><affiliation wicri:level="3"><nlm:affiliation>Department of Respiratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Respiratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author></analytic><series><title level="j">PloS one</title><idno type="eISSN">1932-6203</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Autophagy (physiology)</term><term>Bleomycin</term><term>Disease Models, Animal</term><term>Humans</term><term>Lung (metabolism)</term><term>Lung (pathology)</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Transgenic</term><term>Pulmonary Alveoli (metabolism)</term><term>Pulmonary Alveoli (pathology)</term><term>Pulmonary Fibrosis (chemically induced)</term><term>Pulmonary Fibrosis (metabolism)</term><term>Pulmonary Fibrosis (pathology)</term><term>Signal Transduction (physiology)</term><term>TOR Serine-Threonine Kinases (genetics)</term><term>TOR Serine-Threonine Kinases (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Alvéoles pulmonaires (anatomopathologie)</term><term>Alvéoles pulmonaires (métabolisme)</term><term>Animaux</term><term>Autophagie (physiologie)</term><term>Bléomycine</term><term>Fibrose pulmonaire ()</term><term>Fibrose pulmonaire (anatomopathologie)</term><term>Fibrose pulmonaire (métabolisme)</term><term>Humains</term><term>Modèles animaux de maladie humaine</term><term>Poumon (anatomopathologie)</term><term>Poumon (métabolisme)</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Souris transgéniques</term><term>Sérine-thréonine kinases TOR (génétique)</term><term>Sérine-thréonine kinases TOR (métabolisme)</term><term>Transduction du signal (physiologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>TOR Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>TOR Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Bleomycin</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Alvéoles pulmonaires</term><term>Fibrose pulmonaire</term><term>Poumon</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Pulmonary Fibrosis</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Sérine-thréonine kinases TOR</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lung</term><term>Pulmonary Alveoli</term><term>Pulmonary Fibrosis</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Alvéoles pulmonaires</term><term>Fibrose pulmonaire</term><term>Poumon</term><term>Sérine-thréonine kinases TOR</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lung</term><term>Pulmonary Alveoli</term><term>Pulmonary Fibrosis</term></keywords><keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Autophagie</term><term>Transduction du signal</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Autophagy</term><term>Signal Transduction</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Humans</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Transgenic</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Bléomycine</term><term>Fibrose pulmonaire</term><term>Humains</term><term>Modèles animaux de maladie humaine</term><term>Souris</term><term>Souris de lignée C57BL</term><term>Souris transgéniques</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country><settlement><li>Pékin</li></settlement></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Gui, Yao Song" sort="Gui, Yao Song" uniqKey="Gui Y" first="Yao-Song" last="Gui">Yao-Song Gui</name></noRegion><name sortKey="Cai, Baiqiang" sort="Cai, Baiqiang" uniqKey="Cai B" first="Baiqiang" last="Cai">Baiqiang Cai</name><name sortKey="Chen, Jing Yu" sort="Chen, Jing Yu" uniqKey="Chen J" first="Jing-Yu" last="Chen">Jing-Yu Chen</name><name sortKey="Li, Xue" sort="Li, Xue" uniqKey="Li X" first="Xue" last="Li">Xue Li</name><name sortKey="Ma, Aiping" sort="Ma, Aiping" uniqKey="Ma A" first="Aiping" last="Ma">Aiping Ma</name><name sortKey="Tian, Xinlun" sort="Tian, Xinlun" uniqKey="Tian X" first="Xinlun" last="Tian">Xinlun Tian</name><name sortKey="Wang, Lianmei" sort="Wang, Lianmei" uniqKey="Wang L" first="Lianmei" last="Wang">Lianmei Wang</name><name sortKey="Xu, Kai Feng" sort="Xu, Kai Feng" uniqKey="Xu K" first="Kai-Feng" last="Xu">Kai-Feng Xu</name><name sortKey="Zeng, Ni" sort="Zeng, Ni" uniqKey="Zeng N" first="Ni" last="Zeng">Ni Zeng</name><name sortKey="Zhang, Hongbing" sort="Zhang, Hongbing" uniqKey="Zhang H" first="Hongbing" last="Zhang">Hongbing Zhang</name><name sortKey="Zhang, Ji" sort="Zhang, Ji" uniqKey="Zhang J" first="Ji" last="Zhang">Ji Zhang</name><name sortKey="Zhou, Weixun" sort="Zhou, Weixun" uniqKey="Zhou W" first="Weixun" last="Zhou">Weixun Zhou</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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