Trehalose Alleviates Crystalline Silica-Induced Pulmonary Fibrosis via Activation of the TFEB-Mediated Autophagy-Lysosomal System in Alveolar Macrophages
Identifieur interne : 000013 ( Main/Exploration ); précédent : 000012; suivant : 000014Trehalose Alleviates Crystalline Silica-Induced Pulmonary Fibrosis via Activation of the TFEB-Mediated Autophagy-Lysosomal System in Alveolar Macrophages
Auteurs : Xiu He ; Shi Chen ; Chao Li ; Jiaqi Ban ; Yungeng Wei ; Yangyang He ; Fangwei Liu ; Ying Chen ; Jie ChenSource :
- Cells [ 2073-4409 ] ; 2020.
Abstract
Silicosis is an occupational lung disease characterized by persistent inflammation and irreversible fibrosis. Crystalline silica (CS) particles are mainly phagocytized by alveolar macrophages (AMs), which trigger apoptosis, inflammation, and pulmonary fibrosis. Previously, we found that autophagy-lysosomal system dysfunction in AMs was involved in CS-induced inflammation and fibrosis. Induction of autophagy and lysosomal biogenesis by transcription factor EB (TFEB) nuclear translocation can rescue fibrotic diseases. However, the role of TFEB in silicosis is unknown. In this study, we found that CS induced TFEB nuclear localization and increased TFEB expression in macrophages both in vivo and in vitro. However, TFEB overexpression or treatment with the TFEB activator trehalose (Tre) alleviated lysosomal dysfunction and enhanced autophagic flux. It also reduced apoptosis, inflammatory cytokine levels, and fibrosis. Both pharmacologically inhibition of autophagy and TFEB knockdown in macrophages significantly abolished the antiapoptotic and anti-inflammatory effects elicited by either TFEB overexpression or Tre treatment. In conclusion, these results uncover a protective role of TFEB-mediated autophagy in silicosis. Our study suggests that restoration of autophagy-lysosomal function by Tre-induced TFEB activation may be a novel strategy for the treatment of silicosis.
Url:
DOI: 10.3390/cells9010122
PubMed: 31947943
PubMed Central: 7016807
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Trehalose Alleviates Crystalline Silica-Induced Pulmonary Fibrosis via Activation of the TFEB-Mediated Autophagy-Lysosomal System in Alveolar Macrophages</title><author><name sortKey="He, Xiu" sort="He, Xiu" uniqKey="He X" first="Xiu" last="He">Xiu He</name><affiliation><nlm:aff id="af1-cells-09-00122">Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China;<email>xiuhe_cmu@163.com</email> (X.H.);<email>lichao@cmu.edu.cn</email> (C.L.);<email>17614027841@163.com</email> (J.B.);<email>weiyungeng1736@163.com</email> (Y.W.);<email>heyang129@sina.com</email> (Y.H.);<email>fwliu@cmu.edu.cn</email> (F.L.);<email>ychen25@cmu.edu.cn</email> (Y.C.)</nlm:aff></affiliation></author><author><name sortKey="Chen, Shi" sort="Chen, Shi" uniqKey="Chen S" first="Shi" last="Chen">Shi Chen</name><affiliation><nlm:aff id="af2-cells-09-00122">School of Medicine, Hunan Normal University, No.36 Lushan Road, Changsha 410013, China;<email>chenshonest@163.com</email></nlm:aff></affiliation></author><author><name sortKey="Li, Chao" sort="Li, Chao" uniqKey="Li C" first="Chao" last="Li">Chao Li</name><affiliation><nlm:aff id="af1-cells-09-00122">Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China;<email>xiuhe_cmu@163.com</email> (X.H.);<email>lichao@cmu.edu.cn</email> (C.L.);<email>17614027841@163.com</email> (J.B.);<email>weiyungeng1736@163.com</email> (Y.W.);<email>heyang129@sina.com</email> (Y.H.);<email>fwliu@cmu.edu.cn</email> (F.L.);<email>ychen25@cmu.edu.cn</email> (Y.C.)</nlm:aff></affiliation></author><author><name sortKey="Ban, Jiaqi" sort="Ban, Jiaqi" uniqKey="Ban J" first="Jiaqi" last="Ban">Jiaqi Ban</name><affiliation><nlm:aff id="af1-cells-09-00122">Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China;<email>xiuhe_cmu@163.com</email> (X.H.);<email>lichao@cmu.edu.cn</email> (C.L.);<email>17614027841@163.com</email> (J.B.);<email>weiyungeng1736@163.com</email> (Y.W.);<email>heyang129@sina.com</email> (Y.H.);<email>fwliu@cmu.edu.cn</email> (F.L.);<email>ychen25@cmu.edu.cn</email> (Y.C.)</nlm:aff></affiliation></author><author><name sortKey="Wei, Yungeng" sort="Wei, Yungeng" uniqKey="Wei Y" first="Yungeng" last="Wei">Yungeng Wei</name><affiliation><nlm:aff id="af1-cells-09-00122">Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China;<email>xiuhe_cmu@163.com</email> (X.H.);<email>lichao@cmu.edu.cn</email> (C.L.);<email>17614027841@163.com</email> (J.B.);<email>weiyungeng1736@163.com</email> (Y.W.);<email>heyang129@sina.com</email> (Y.H.);<email>fwliu@cmu.edu.cn</email> (F.L.);<email>ychen25@cmu.edu.cn</email> (Y.C.)</nlm:aff></affiliation></author><author><name sortKey="He, Yangyang" sort="He, Yangyang" uniqKey="He Y" first="Yangyang" last="He">Yangyang He</name><affiliation><nlm:aff id="af1-cells-09-00122">Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China;<email>xiuhe_cmu@163.com</email> (X.H.);<email>lichao@cmu.edu.cn</email> (C.L.);<email>17614027841@163.com</email> (J.B.);<email>weiyungeng1736@163.com</email> (Y.W.);<email>heyang129@sina.com</email> (Y.H.);<email>fwliu@cmu.edu.cn</email> (F.L.);<email>ychen25@cmu.edu.cn</email> (Y.C.)</nlm:aff></affiliation></author><author><name sortKey="Liu, Fangwei" sort="Liu, Fangwei" uniqKey="Liu F" first="Fangwei" last="Liu">Fangwei Liu</name><affiliation><nlm:aff id="af1-cells-09-00122">Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China;<email>xiuhe_cmu@163.com</email> (X.H.);<email>lichao@cmu.edu.cn</email> (C.L.);<email>17614027841@163.com</email> (J.B.);<email>weiyungeng1736@163.com</email> (Y.W.);<email>heyang129@sina.com</email> (Y.H.);<email>fwliu@cmu.edu.cn</email> (F.L.);<email>ychen25@cmu.edu.cn</email> (Y.C.)</nlm:aff></affiliation></author><author><name sortKey="Chen, Ying" sort="Chen, Ying" uniqKey="Chen Y" first="Ying" last="Chen">Ying Chen</name><affiliation><nlm:aff id="af1-cells-09-00122">Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China;<email>xiuhe_cmu@163.com</email> (X.H.);<email>lichao@cmu.edu.cn</email> (C.L.);<email>17614027841@163.com</email> (J.B.);<email>weiyungeng1736@163.com</email> (Y.W.);<email>heyang129@sina.com</email> (Y.H.);<email>fwliu@cmu.edu.cn</email> (F.L.);<email>ychen25@cmu.edu.cn</email> (Y.C.)</nlm:aff></affiliation></author><author><name sortKey="Chen, Jie" sort="Chen, Jie" uniqKey="Chen J" first="Jie" last="Chen">Jie Chen</name><affiliation><nlm:aff id="af1-cells-09-00122">Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China;<email>xiuhe_cmu@163.com</email> (X.H.);<email>lichao@cmu.edu.cn</email> (C.L.);<email>17614027841@163.com</email> (J.B.);<email>weiyungeng1736@163.com</email> (Y.W.);<email>heyang129@sina.com</email> (Y.H.);<email>fwliu@cmu.edu.cn</email> (F.L.);<email>ychen25@cmu.edu.cn</email> (Y.C.)</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31947943</idno><idno type="pmc">7016807</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016807</idno><idno type="RBID">PMC:7016807</idno><idno type="doi">10.3390/cells9010122</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000479</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" 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id="af1-cells-09-00122">Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China;<email>xiuhe_cmu@163.com</email> (X.H.);<email>lichao@cmu.edu.cn</email> (C.L.);<email>17614027841@163.com</email> (J.B.);<email>weiyungeng1736@163.com</email> (Y.W.);<email>heyang129@sina.com</email> (Y.H.);<email>fwliu@cmu.edu.cn</email> (F.L.);<email>ychen25@cmu.edu.cn</email> (Y.C.)</nlm:aff></affiliation></author><author><name sortKey="Chen, Shi" sort="Chen, Shi" uniqKey="Chen S" first="Shi" last="Chen">Shi Chen</name><affiliation><nlm:aff id="af2-cells-09-00122">School of Medicine, Hunan Normal University, No.36 Lushan Road, Changsha 410013, China;<email>chenshonest@163.com</email></nlm:aff></affiliation></author><author><name sortKey="Li, Chao" sort="Li, Chao" uniqKey="Li C" first="Chao" last="Li">Chao Li</name><affiliation><nlm:aff id="af1-cells-09-00122">Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China;<email>xiuhe_cmu@163.com</email> (X.H.);<email>lichao@cmu.edu.cn</email> (C.L.);<email>17614027841@163.com</email> (J.B.);<email>weiyungeng1736@163.com</email> (Y.W.);<email>heyang129@sina.com</email> (Y.H.);<email>fwliu@cmu.edu.cn</email> (F.L.);<email>ychen25@cmu.edu.cn</email> (Y.C.)</nlm:aff></affiliation></author><author><name sortKey="Ban, Jiaqi" sort="Ban, Jiaqi" uniqKey="Ban J" first="Jiaqi" last="Ban">Jiaqi Ban</name><affiliation><nlm:aff id="af1-cells-09-00122">Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China;<email>xiuhe_cmu@163.com</email> (X.H.);<email>lichao@cmu.edu.cn</email> (C.L.);<email>17614027841@163.com</email> (J.B.);<email>weiyungeng1736@163.com</email> (Y.W.);<email>heyang129@sina.com</email> (Y.H.);<email>fwliu@cmu.edu.cn</email> (F.L.);<email>ychen25@cmu.edu.cn</email> (Y.C.)</nlm:aff></affiliation></author><author><name sortKey="Wei, Yungeng" sort="Wei, Yungeng" uniqKey="Wei Y" first="Yungeng" last="Wei">Yungeng Wei</name><affiliation><nlm:aff id="af1-cells-09-00122">Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China;<email>xiuhe_cmu@163.com</email> (X.H.);<email>lichao@cmu.edu.cn</email> (C.L.);<email>17614027841@163.com</email> (J.B.);<email>weiyungeng1736@163.com</email> (Y.W.);<email>heyang129@sina.com</email> (Y.H.);<email>fwliu@cmu.edu.cn</email> (F.L.);<email>ychen25@cmu.edu.cn</email> (Y.C.)</nlm:aff></affiliation></author><author><name sortKey="He, Yangyang" sort="He, Yangyang" uniqKey="He Y" first="Yangyang" last="He">Yangyang He</name><affiliation><nlm:aff id="af1-cells-09-00122">Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China;<email>xiuhe_cmu@163.com</email> (X.H.);<email>lichao@cmu.edu.cn</email> (C.L.);<email>17614027841@163.com</email> (J.B.);<email>weiyungeng1736@163.com</email> (Y.W.);<email>heyang129@sina.com</email> (Y.H.);<email>fwliu@cmu.edu.cn</email> (F.L.);<email>ychen25@cmu.edu.cn</email> (Y.C.)</nlm:aff></affiliation></author><author><name sortKey="Liu, Fangwei" sort="Liu, Fangwei" uniqKey="Liu F" first="Fangwei" last="Liu">Fangwei Liu</name><affiliation><nlm:aff id="af1-cells-09-00122">Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China;<email>xiuhe_cmu@163.com</email> (X.H.);<email>lichao@cmu.edu.cn</email> (C.L.);<email>17614027841@163.com</email> (J.B.);<email>weiyungeng1736@163.com</email> (Y.W.);<email>heyang129@sina.com</email> (Y.H.);<email>fwliu@cmu.edu.cn</email> (F.L.);<email>ychen25@cmu.edu.cn</email> (Y.C.)</nlm:aff></affiliation></author><author><name sortKey="Chen, Ying" sort="Chen, Ying" uniqKey="Chen Y" first="Ying" last="Chen">Ying Chen</name><affiliation><nlm:aff id="af1-cells-09-00122">Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China;<email>xiuhe_cmu@163.com</email> (X.H.);<email>lichao@cmu.edu.cn</email> (C.L.);<email>17614027841@163.com</email> (J.B.);<email>weiyungeng1736@163.com</email> (Y.W.);<email>heyang129@sina.com</email> (Y.H.);<email>fwliu@cmu.edu.cn</email> (F.L.);<email>ychen25@cmu.edu.cn</email> (Y.C.)</nlm:aff></affiliation></author><author><name sortKey="Chen, Jie" sort="Chen, Jie" uniqKey="Chen J" first="Jie" last="Chen">Jie Chen</name><affiliation><nlm:aff id="af1-cells-09-00122">Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China;<email>xiuhe_cmu@163.com</email> (X.H.);<email>lichao@cmu.edu.cn</email> (C.L.);<email>17614027841@163.com</email> (J.B.);<email>weiyungeng1736@163.com</email> (Y.W.);<email>heyang129@sina.com</email> (Y.H.);<email>fwliu@cmu.edu.cn</email> (F.L.);<email>ychen25@cmu.edu.cn</email> (Y.C.)</nlm:aff></affiliation></author></analytic><series><title level="j">Cells</title><idno type="eISSN">2073-4409</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Silicosis is an occupational lung disease characterized by persistent inflammation and irreversible fibrosis. Crystalline silica (CS) particles are mainly phagocytized by alveolar macrophages (AMs), which trigger apoptosis, inflammation, and pulmonary fibrosis. Previously, we found that autophagy-lysosomal system dysfunction in AMs was involved in CS-induced inflammation and fibrosis. Induction of autophagy and lysosomal biogenesis by transcription factor EB (TFEB) nuclear translocation can rescue fibrotic diseases. However, the role of TFEB in silicosis is unknown. In this study, we found that CS induced TFEB nuclear localization and increased TFEB expression in macrophages both in vivo and in vitro. However, TFEB overexpression or treatment with the TFEB activator trehalose (Tre) alleviated lysosomal dysfunction and enhanced autophagic flux. It also reduced apoptosis, inflammatory cytokine levels, and fibrosis. Both pharmacologically inhibition of autophagy and TFEB knockdown in macrophages significantly abolished the antiapoptotic and anti-inflammatory effects elicited by either TFEB overexpression or Tre treatment. In conclusion, these results uncover a protective role of TFEB-mediated autophagy in silicosis. Our study suggests that restoration of autophagy-lysosomal function by Tre-induced TFEB activation may be a novel strategy for the treatment of silicosis.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Leung, C C" uniqKey="Leung C">C.C. Leung</name></author><author><name sortKey="Yu, I T S" uniqKey="Yu I">I.T.S. Yu</name></author><author><name sortKey="Chen, W" uniqKey="Chen W">W. Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, C" uniqKey="Li C">C. Li</name></author><author><name sortKey="Du, S" uniqKey="Du S">S. Du</name></author><author><name sortKey="Lu, Y" uniqKey="Lu Y">Y. 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Baehrecke</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list></list><tree><noCountry><name sortKey="Ban, Jiaqi" sort="Ban, Jiaqi" uniqKey="Ban J" first="Jiaqi" last="Ban">Jiaqi Ban</name><name sortKey="Chen, Jie" sort="Chen, Jie" uniqKey="Chen J" first="Jie" last="Chen">Jie Chen</name><name sortKey="Chen, Shi" sort="Chen, Shi" uniqKey="Chen S" first="Shi" last="Chen">Shi Chen</name><name sortKey="Chen, Ying" sort="Chen, Ying" uniqKey="Chen Y" first="Ying" last="Chen">Ying Chen</name><name sortKey="He, Xiu" sort="He, Xiu" uniqKey="He X" first="Xiu" last="He">Xiu He</name><name sortKey="He, Yangyang" sort="He, Yangyang" uniqKey="He Y" first="Yangyang" last="He">Yangyang He</name><name sortKey="Li, Chao" sort="Li, Chao" uniqKey="Li C" first="Chao" last="Li">Chao Li</name><name sortKey="Liu, Fangwei" sort="Liu, Fangwei" uniqKey="Liu F" first="Fangwei" last="Liu">Fangwei Liu</name><name sortKey="Wei, Yungeng" sort="Wei, Yungeng" uniqKey="Wei Y" first="Yungeng" last="Wei">Yungeng Wei</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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