Autophagy affects hepatic fibrosis progression by regulating macrophage polarization and exosome secretion
Background In this study, the role of autophagy in hepatic fibrosis and its effects on macrophage polarization and exosomes (EVs) were verified by establishing hepatic fibrosis model and co‐culture model, providing evidence for treatment. Methods In this study, CCL4 was used to establish hepatic fib...
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| Veröffentlicht in: | Environmental toxicology 2023-07, Vol.38 (7), p.1665-1677 |
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| creator | Hu, Zongqiang Chen, Gang Yan, Chuntao Li, Zhiqiang Wu, Tao Li, Li Zhang, Shengning |
| description | Background
In this study, the role of autophagy in hepatic fibrosis and its effects on macrophage polarization and exosomes (EVs) were verified by establishing hepatic fibrosis model and co‐culture model, providing evidence for treatment.
Methods
In this study, CCL4 was used to establish hepatic fibrosis model. The morphology and purity of exosomes (EVs) were verified by transmission electron microscopy, western blotting (WB), and nanoparticle tracing analysis (NTA). Real‐time quantitative PCR (qRT‐PCR), WB and enzyme‐linked immunoadsorption (ELISA) were used to detect hepatic fibrosis markers, macrophage polarization markers and liver injury markers. Histopathological assays were used to verify the liver injury morphology in different groups. The cell co‐culture model and hepatic fibrosis model were constructed to verify the expression of miR‐423‐5p.
Results
Hepatic fibrosis model showed that CCL4 promoted early autophagy increase but inhibited autophagy flux in liver. mRFP‐GFP‐LC3 detection showed that both LPS group and Baf group inhibited autophagy flux. This inhibitory effect was reversed by Rap combination therapy. The M1/M2 markers of macrophage polarization were further tested, and it was found that LPS and Baf could promote M1 polarization and inhibit M2 polarization. Rap processing reverses this phenomenon. These data suggest that autophagy can regulate the polarization process of liver macrophages. WB and NTA showed that LPS induced EVs generation. In addition, LPS‐induced EVs could promote HSC proliferation, cell cycle, migration, and the expression of fibrosis markers. Macrophage‐EVs could affect the fibrosis process of stellate cells through the secretion of miR‐423a‐5p expression. The hepatic fibrosis model was further established to verify the regulation of autophagy and EVs on the fibrosis process.
Conclusion
This study was showed that autophagy could regulate fibrosis by promoting HSC activation by regulating macrophage polarization and exosome secretion. |
| doi_str_mv | 10.1002/tox.23795 |
| format | Article |
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In this study, the role of autophagy in hepatic fibrosis and its effects on macrophage polarization and exosomes (EVs) were verified by establishing hepatic fibrosis model and co‐culture model, providing evidence for treatment.
Methods
In this study, CCL4 was used to establish hepatic fibrosis model. The morphology and purity of exosomes (EVs) were verified by transmission electron microscopy, western blotting (WB), and nanoparticle tracing analysis (NTA). Real‐time quantitative PCR (qRT‐PCR), WB and enzyme‐linked immunoadsorption (ELISA) were used to detect hepatic fibrosis markers, macrophage polarization markers and liver injury markers. Histopathological assays were used to verify the liver injury morphology in different groups. The cell co‐culture model and hepatic fibrosis model were constructed to verify the expression of miR‐423‐5p.
Results
Hepatic fibrosis model showed that CCL4 promoted early autophagy increase but inhibited autophagy flux in liver. mRFP‐GFP‐LC3 detection showed that both LPS group and Baf group inhibited autophagy flux. This inhibitory effect was reversed by Rap combination therapy. The M1/M2 markers of macrophage polarization were further tested, and it was found that LPS and Baf could promote M1 polarization and inhibit M2 polarization. Rap processing reverses this phenomenon. These data suggest that autophagy can regulate the polarization process of liver macrophages. WB and NTA showed that LPS induced EVs generation. In addition, LPS‐induced EVs could promote HSC proliferation, cell cycle, migration, and the expression of fibrosis markers. Macrophage‐EVs could affect the fibrosis process of stellate cells through the secretion of miR‐423a‐5p expression. The hepatic fibrosis model was further established to verify the regulation of autophagy and EVs on the fibrosis process.
Conclusion
This study was showed that autophagy could regulate fibrosis by promoting HSC activation by regulating macrophage polarization and exosome secretion.</description><identifier>ISSN: 1520-4081</identifier><identifier>EISSN: 1522-7278</identifier><identifier>DOI: 10.1002/tox.23795</identifier><identifier>PMID: 37186334</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Autophagy ; Cell activation ; Cell culture ; Cell cycle ; Cytology ; Electron microscopy ; ELISA ; Enzyme-linked immunosorbent assay ; exosome ; Exosomes ; Fibrosis ; hepatic fibrosis ; hepatic stellate cells ; Histopathology ; Leukocyte migration ; Lipopolysaccharides ; Liver ; macrophage ; Macrophages ; Morphology ; Nanoparticles ; Nucleotide sequence ; Polarization ; Polymerase chain reaction ; Proliferation ; Secretion ; Stellate cells ; Transmission electron microscopy ; Western blotting</subject><ispartof>Environmental toxicology, 2023-07, Vol.38 (7), p.1665-1677</ispartof><rights>2023 The Authors. published by Wiley Periodicals LLC.</rights><rights>2023 The Authors. Environmental Toxicology published by Wiley Periodicals LLC.</rights><rights>2023. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3885-ece1096e33be38b057e5811cd86df77551772360423e7207d6d3d0ccfde001503</citedby><cites>FETCH-LOGICAL-c3885-ece1096e33be38b057e5811cd86df77551772360423e7207d6d3d0ccfde001503</cites><orcidid>0000-0001-6133-0132</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Ftox.23795$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Ftox.23795$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37186334$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hu, Zongqiang</creatorcontrib><creatorcontrib>Chen, Gang</creatorcontrib><creatorcontrib>Yan, Chuntao</creatorcontrib><creatorcontrib>Li, Zhiqiang</creatorcontrib><creatorcontrib>Wu, Tao</creatorcontrib><creatorcontrib>Li, Li</creatorcontrib><creatorcontrib>Zhang, Shengning</creatorcontrib><title>Autophagy affects hepatic fibrosis progression by regulating macrophage polarization and exosome secretion</title><title>Environmental toxicology</title><addtitle>Environ Toxicol</addtitle><description>Background
In this study, the role of autophagy in hepatic fibrosis and its effects on macrophage polarization and exosomes (EVs) were verified by establishing hepatic fibrosis model and co‐culture model, providing evidence for treatment.
Methods
In this study, CCL4 was used to establish hepatic fibrosis model. The morphology and purity of exosomes (EVs) were verified by transmission electron microscopy, western blotting (WB), and nanoparticle tracing analysis (NTA). Real‐time quantitative PCR (qRT‐PCR), WB and enzyme‐linked immunoadsorption (ELISA) were used to detect hepatic fibrosis markers, macrophage polarization markers and liver injury markers. Histopathological assays were used to verify the liver injury morphology in different groups. The cell co‐culture model and hepatic fibrosis model were constructed to verify the expression of miR‐423‐5p.
Results
Hepatic fibrosis model showed that CCL4 promoted early autophagy increase but inhibited autophagy flux in liver. mRFP‐GFP‐LC3 detection showed that both LPS group and Baf group inhibited autophagy flux. This inhibitory effect was reversed by Rap combination therapy. The M1/M2 markers of macrophage polarization were further tested, and it was found that LPS and Baf could promote M1 polarization and inhibit M2 polarization. Rap processing reverses this phenomenon. These data suggest that autophagy can regulate the polarization process of liver macrophages. WB and NTA showed that LPS induced EVs generation. In addition, LPS‐induced EVs could promote HSC proliferation, cell cycle, migration, and the expression of fibrosis markers. Macrophage‐EVs could affect the fibrosis process of stellate cells through the secretion of miR‐423a‐5p expression. The hepatic fibrosis model was further established to verify the regulation of autophagy and EVs on the fibrosis process.
Conclusion
This study was showed that autophagy could regulate fibrosis by promoting HSC activation by regulating macrophage polarization and exosome secretion.</description><subject>Autophagy</subject><subject>Cell activation</subject><subject>Cell culture</subject><subject>Cell cycle</subject><subject>Cytology</subject><subject>Electron microscopy</subject><subject>ELISA</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>exosome</subject><subject>Exosomes</subject><subject>Fibrosis</subject><subject>hepatic fibrosis</subject><subject>hepatic stellate cells</subject><subject>Histopathology</subject><subject>Leukocyte migration</subject><subject>Lipopolysaccharides</subject><subject>Liver</subject><subject>macrophage</subject><subject>Macrophages</subject><subject>Morphology</subject><subject>Nanoparticles</subject><subject>Nucleotide sequence</subject><subject>Polarization</subject><subject>Polymerase chain reaction</subject><subject>Proliferation</subject><subject>Secretion</subject><subject>Stellate cells</subject><subject>Transmission electron microscopy</subject><subject>Western blotting</subject><issn>1520-4081</issn><issn>1522-7278</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><recordid>eNp10c9LwzAUB_Agis7pwX9AAl70UJcfTZMdx_AXCLtM8FbS9HXraJuatLj515v90IPgKeHxyZf38hC6ouSeEsJGnV3fMy7H4ggNqGAskkyq492dRDFR9Ayde78ihIwTkZyiMy6pSjiPB2g16TvbLvVig3VRgOk8XkKru9Lgosyc9aXHrbMLB96XtsHZBjtY9FUQzQLX2rjda8CtrbQrv0I9KN3kGNbW2xqwB-NgW71AJ4WuPFweziF6e3yYT5-j19nTy3TyGhmulIjAAA19AucZcJURIUEoSk2ukryQUggqJeMJiRkHyYjMk5znxJgiB0KoIHyIbve5oe-PHnyX1qU3UFW6Adv7lCkaCzaOZRLozR-6sr1rQndBMRlTyhgL6m6vwrDeOyjS1pW1dpuUknS7gDQsIN0tINjrQ2Kf1ZD_yp8fD2C0B59lBZv_k9L57H0f-Q0p9JDJ</recordid><startdate>202307</startdate><enddate>202307</enddate><creator>Hu, Zongqiang</creator><creator>Chen, Gang</creator><creator>Yan, Chuntao</creator><creator>Li, Zhiqiang</creator><creator>Wu, Tao</creator><creator>Li, Li</creator><creator>Zhang, Shengning</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QH</scope><scope>7ST</scope><scope>7TN</scope><scope>7U7</scope><scope>7UA</scope><scope>C1K</scope><scope>F1W</scope><scope>H97</scope><scope>K9.</scope><scope>L.G</scope><scope>M7N</scope><scope>SOI</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-6133-0132</orcidid></search><sort><creationdate>202307</creationdate><title>Autophagy affects hepatic fibrosis progression by regulating macrophage polarization and exosome secretion</title><author>Hu, Zongqiang ; Chen, Gang ; Yan, Chuntao ; Li, Zhiqiang ; Wu, Tao ; Li, Li ; Zhang, Shengning</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3885-ece1096e33be38b057e5811cd86df77551772360423e7207d6d3d0ccfde001503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Autophagy</topic><topic>Cell activation</topic><topic>Cell culture</topic><topic>Cell cycle</topic><topic>Cytology</topic><topic>Electron microscopy</topic><topic>ELISA</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>exosome</topic><topic>Exosomes</topic><topic>Fibrosis</topic><topic>hepatic fibrosis</topic><topic>hepatic stellate cells</topic><topic>Histopathology</topic><topic>Leukocyte migration</topic><topic>Lipopolysaccharides</topic><topic>Liver</topic><topic>macrophage</topic><topic>Macrophages</topic><topic>Morphology</topic><topic>Nanoparticles</topic><topic>Nucleotide sequence</topic><topic>Polarization</topic><topic>Polymerase chain reaction</topic><topic>Proliferation</topic><topic>Secretion</topic><topic>Stellate cells</topic><topic>Transmission electron microscopy</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hu, Zongqiang</creatorcontrib><creatorcontrib>Chen, Gang</creatorcontrib><creatorcontrib>Yan, Chuntao</creatorcontrib><creatorcontrib>Li, Zhiqiang</creatorcontrib><creatorcontrib>Wu, Tao</creatorcontrib><creatorcontrib>Li, Li</creatorcontrib><creatorcontrib>Zhang, Shengning</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Aqualine</collection><collection>Environment Abstracts</collection><collection>Oceanic Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Water Resources Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Environmental toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hu, Zongqiang</au><au>Chen, Gang</au><au>Yan, Chuntao</au><au>Li, Zhiqiang</au><au>Wu, Tao</au><au>Li, Li</au><au>Zhang, Shengning</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Autophagy affects hepatic fibrosis progression by regulating macrophage polarization and exosome secretion</atitle><jtitle>Environmental toxicology</jtitle><addtitle>Environ Toxicol</addtitle><date>2023-07</date><risdate>2023</risdate><volume>38</volume><issue>7</issue><spage>1665</spage><epage>1677</epage><pages>1665-1677</pages><issn>1520-4081</issn><eissn>1522-7278</eissn><abstract>Background
In this study, the role of autophagy in hepatic fibrosis and its effects on macrophage polarization and exosomes (EVs) were verified by establishing hepatic fibrosis model and co‐culture model, providing evidence for treatment.
Methods
In this study, CCL4 was used to establish hepatic fibrosis model. The morphology and purity of exosomes (EVs) were verified by transmission electron microscopy, western blotting (WB), and nanoparticle tracing analysis (NTA). Real‐time quantitative PCR (qRT‐PCR), WB and enzyme‐linked immunoadsorption (ELISA) were used to detect hepatic fibrosis markers, macrophage polarization markers and liver injury markers. Histopathological assays were used to verify the liver injury morphology in different groups. The cell co‐culture model and hepatic fibrosis model were constructed to verify the expression of miR‐423‐5p.
Results
Hepatic fibrosis model showed that CCL4 promoted early autophagy increase but inhibited autophagy flux in liver. mRFP‐GFP‐LC3 detection showed that both LPS group and Baf group inhibited autophagy flux. This inhibitory effect was reversed by Rap combination therapy. The M1/M2 markers of macrophage polarization were further tested, and it was found that LPS and Baf could promote M1 polarization and inhibit M2 polarization. Rap processing reverses this phenomenon. These data suggest that autophagy can regulate the polarization process of liver macrophages. WB and NTA showed that LPS induced EVs generation. In addition, LPS‐induced EVs could promote HSC proliferation, cell cycle, migration, and the expression of fibrosis markers. Macrophage‐EVs could affect the fibrosis process of stellate cells through the secretion of miR‐423a‐5p expression. The hepatic fibrosis model was further established to verify the regulation of autophagy and EVs on the fibrosis process.
Conclusion
This study was showed that autophagy could regulate fibrosis by promoting HSC activation by regulating macrophage polarization and exosome secretion.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>37186334</pmid><doi>10.1002/tox.23795</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-6133-0132</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Autophagy Cell activation Cell culture Cell cycle Cytology Electron microscopy ELISA Enzyme-linked immunosorbent assay exosome Exosomes Fibrosis hepatic fibrosis hepatic stellate cells Histopathology Leukocyte migration Lipopolysaccharides Liver macrophage Macrophages Morphology Nanoparticles Nucleotide sequence Polarization Polymerase chain reaction Proliferation Secretion Stellate cells Transmission electron microscopy Western blotting |
| title | Autophagy affects hepatic fibrosis progression by regulating macrophage polarization and exosome secretion |
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