Fluorofenidone Attenuates Renal Interstitial Fibrosis by Enhancing Autophagy and Retaining Mitochondrial Function
Background Fluorofenidone (AKF-PD) is a novel pyridone agent and has potent anti-NLRP3 inflammasome and anti-fibrotic activities. However, the mechanisms underlying its pharmacological actions are not fully understood. Methods A renal fibrosis rat model was established by the unilateral ureteral obs...
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| Veröffentlicht in: | Cell biochemistry and biophysics 2023-12, Vol.81 (4), p.777-785 |
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| description | Background
Fluorofenidone (AKF-PD) is a novel pyridone agent and has potent anti-NLRP3 inflammasome and anti-fibrotic activities. However, the mechanisms underlying its pharmacological actions are not fully understood.
Methods
A renal fibrosis rat model was established by the unilateral ureteral obstruction (UUO) procedure and the rats were randomized and treated with, or without, AKF-PD for 3 and 7 days. The levels of renal fibrosis, NLRP3 inflammasome activation, mitochondrial function, and autophagy were tested in rat kidney tissues. Macrophages following lipopolysaccharides (LPS) and adenosine 5′-triphosphate (ATP) stimulation were examined by Western blot, spectrophotometry, and TEM.
Results
Compared with the untreated UUO rats, AKF-PD treatment significantly mitigated the UUO procedure-induced renal fibrosis in rats. AKF-PD treatment decreased mitochondrial dysfunction and IL-Iβ and caspase-1 expression in rat kidney tissues and reduced mitochondrial reactive oxygen species production in activated macrophages. Mechanistically, AKF-PD treatment significantly attenuated the PI3K/AKT/mTOR signaling, increased Beclin-1 and LC3 II expression and autophagosome formation, and ameliorated the mitochondrial damage in renal tissues and activated macrophages.
Conclusion
The results indicated that AKF-PD treatment inhibited renal interstitial fibrosis by regulating the autophagy-mitochondria-NLRP3 inflammasome pathway. |
| doi_str_mv | 10.1007/s12013-023-01176-7 |
| format | Article |
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Fluorofenidone (AKF-PD) is a novel pyridone agent and has potent anti-NLRP3 inflammasome and anti-fibrotic activities. However, the mechanisms underlying its pharmacological actions are not fully understood.
Methods
A renal fibrosis rat model was established by the unilateral ureteral obstruction (UUO) procedure and the rats were randomized and treated with, or without, AKF-PD for 3 and 7 days. The levels of renal fibrosis, NLRP3 inflammasome activation, mitochondrial function, and autophagy were tested in rat kidney tissues. Macrophages following lipopolysaccharides (LPS) and adenosine 5′-triphosphate (ATP) stimulation were examined by Western blot, spectrophotometry, and TEM.
Results
Compared with the untreated UUO rats, AKF-PD treatment significantly mitigated the UUO procedure-induced renal fibrosis in rats. AKF-PD treatment decreased mitochondrial dysfunction and IL-Iβ and caspase-1 expression in rat kidney tissues and reduced mitochondrial reactive oxygen species production in activated macrophages. Mechanistically, AKF-PD treatment significantly attenuated the PI3K/AKT/mTOR signaling, increased Beclin-1 and LC3 II expression and autophagosome formation, and ameliorated the mitochondrial damage in renal tissues and activated macrophages.
Conclusion
The results indicated that AKF-PD treatment inhibited renal interstitial fibrosis by regulating the autophagy-mitochondria-NLRP3 inflammasome pathway.</description><identifier>ISSN: 1085-9195</identifier><identifier>EISSN: 1559-0283</identifier><identifier>DOI: 10.1007/s12013-023-01176-7</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>1-Phosphatidylinositol 3-kinase ; Adenosine ; AKT protein ; Animal tissues ; Autophagy ; Biochemistry ; Biological and Medical Physics ; Biomedical and Life Sciences ; Biophysics ; Biotechnology ; Caspase-1 ; Cell Biology ; Fibrosis ; Inflammasomes ; Kidneys ; Life Sciences ; Lipopolysaccharides ; Macrophages ; Mitochondria ; Original Paper ; Pharmacology/Toxicology ; Reactive oxygen species ; Spectrophotometry ; TOR protein</subject><ispartof>Cell biochemistry and biophysics, 2023-12, Vol.81 (4), p.777-785</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c303t-f7cad91ffd8e6e7a5c97c055194cd0b8b2cdf800e12a0c6050a8553c31f42a273</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12013-023-01176-7$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12013-023-01176-7$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids></links><search><creatorcontrib>Liu, Wenlin</creatorcontrib><creatorcontrib>Zhou, Hongli</creatorcontrib><creatorcontrib>Dong, Haonan</creatorcontrib><creatorcontrib>Xing, Di</creatorcontrib><creatorcontrib>Lu, Miaomiao</creatorcontrib><title>Fluorofenidone Attenuates Renal Interstitial Fibrosis by Enhancing Autophagy and Retaining Mitochondrial Function</title><title>Cell biochemistry and biophysics</title><addtitle>Cell Biochem Biophys</addtitle><description>Background
Fluorofenidone (AKF-PD) is a novel pyridone agent and has potent anti-NLRP3 inflammasome and anti-fibrotic activities. However, the mechanisms underlying its pharmacological actions are not fully understood.
Methods
A renal fibrosis rat model was established by the unilateral ureteral obstruction (UUO) procedure and the rats were randomized and treated with, or without, AKF-PD for 3 and 7 days. The levels of renal fibrosis, NLRP3 inflammasome activation, mitochondrial function, and autophagy were tested in rat kidney tissues. Macrophages following lipopolysaccharides (LPS) and adenosine 5′-triphosphate (ATP) stimulation were examined by Western blot, spectrophotometry, and TEM.
Results
Compared with the untreated UUO rats, AKF-PD treatment significantly mitigated the UUO procedure-induced renal fibrosis in rats. AKF-PD treatment decreased mitochondrial dysfunction and IL-Iβ and caspase-1 expression in rat kidney tissues and reduced mitochondrial reactive oxygen species production in activated macrophages. Mechanistically, AKF-PD treatment significantly attenuated the PI3K/AKT/mTOR signaling, increased Beclin-1 and LC3 II expression and autophagosome formation, and ameliorated the mitochondrial damage in renal tissues and activated macrophages.
Conclusion
The results indicated that AKF-PD treatment inhibited renal interstitial fibrosis by regulating the autophagy-mitochondria-NLRP3 inflammasome pathway.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>Adenosine</subject><subject>AKT protein</subject><subject>Animal tissues</subject><subject>Autophagy</subject><subject>Biochemistry</subject><subject>Biological and Medical Physics</subject><subject>Biomedical and Life Sciences</subject><subject>Biophysics</subject><subject>Biotechnology</subject><subject>Caspase-1</subject><subject>Cell Biology</subject><subject>Fibrosis</subject><subject>Inflammasomes</subject><subject>Kidneys</subject><subject>Life Sciences</subject><subject>Lipopolysaccharides</subject><subject>Macrophages</subject><subject>Mitochondria</subject><subject>Original Paper</subject><subject>Pharmacology/Toxicology</subject><subject>Reactive oxygen species</subject><subject>Spectrophotometry</subject><subject>TOR protein</subject><issn>1085-9195</issn><issn>1559-0283</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>BENPR</sourceid><recordid>eNp9kcFLwzAUxosoOKf_gKeCFy_Vl7Rp0uMYmw4mgug5pGm6ZXTJlqSH_femqyB48BBe8vh9H3nvS5J7BE8IgD57hAHlGeB4EKJlRi-SCSKkii2WX8Y7MJJVqCLXyY33OwCMoSgmyXHZ9dbZVhndWKPSWQjK9CIon34oI7p0ZYJyPuig42Opa2e99ml9ShdmK4zUZpPO-mAPW7E5pcI0URaENkP_TQcrt9Y07qztjQzamtvkqhWdV3c_dZp8LRef89ds_f6yms_WmcwhD1lLpWgq1LYNU6WigsiKSiAEVYVsoGY1lk3LABTCAmQJBAQjJJc5agssMM2nyePoe3D22Csf-F57qbpOGGV7zzErWdwarlhEH_6gO9u7OP1AMUwrzNBA4ZGScQfeqZYfnN4Ld-II-JACH1PgMQV-ToEPv8hHkY-w2Sj3a_2P6ht1xYvy</recordid><startdate>20231201</startdate><enddate>20231201</enddate><creator>Liu, Wenlin</creator><creator>Zhou, Hongli</creator><creator>Dong, Haonan</creator><creator>Xing, Di</creator><creator>Lu, Miaomiao</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20231201</creationdate><title>Fluorofenidone Attenuates Renal Interstitial Fibrosis by Enhancing Autophagy and Retaining Mitochondrial Function</title><author>Liu, Wenlin ; Zhou, Hongli ; Dong, Haonan ; Xing, Di ; Lu, Miaomiao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c303t-f7cad91ffd8e6e7a5c97c055194cd0b8b2cdf800e12a0c6050a8553c31f42a273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>Adenosine</topic><topic>AKT protein</topic><topic>Animal tissues</topic><topic>Autophagy</topic><topic>Biochemistry</topic><topic>Biological and Medical Physics</topic><topic>Biomedical and Life Sciences</topic><topic>Biophysics</topic><topic>Biotechnology</topic><topic>Caspase-1</topic><topic>Cell Biology</topic><topic>Fibrosis</topic><topic>Inflammasomes</topic><topic>Kidneys</topic><topic>Life Sciences</topic><topic>Lipopolysaccharides</topic><topic>Macrophages</topic><topic>Mitochondria</topic><topic>Original Paper</topic><topic>Pharmacology/Toxicology</topic><topic>Reactive oxygen species</topic><topic>Spectrophotometry</topic><topic>TOR protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Wenlin</creatorcontrib><creatorcontrib>Zhou, Hongli</creatorcontrib><creatorcontrib>Dong, Haonan</creatorcontrib><creatorcontrib>Xing, Di</creatorcontrib><creatorcontrib>Lu, Miaomiao</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cell biochemistry and biophysics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Wenlin</au><au>Zhou, Hongli</au><au>Dong, Haonan</au><au>Xing, Di</au><au>Lu, Miaomiao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fluorofenidone Attenuates Renal Interstitial Fibrosis by Enhancing Autophagy and Retaining Mitochondrial Function</atitle><jtitle>Cell biochemistry and biophysics</jtitle><stitle>Cell Biochem Biophys</stitle><date>2023-12-01</date><risdate>2023</risdate><volume>81</volume><issue>4</issue><spage>777</spage><epage>785</epage><pages>777-785</pages><issn>1085-9195</issn><eissn>1559-0283</eissn><abstract>Background
Fluorofenidone (AKF-PD) is a novel pyridone agent and has potent anti-NLRP3 inflammasome and anti-fibrotic activities. However, the mechanisms underlying its pharmacological actions are not fully understood.
Methods
A renal fibrosis rat model was established by the unilateral ureteral obstruction (UUO) procedure and the rats were randomized and treated with, or without, AKF-PD for 3 and 7 days. The levels of renal fibrosis, NLRP3 inflammasome activation, mitochondrial function, and autophagy were tested in rat kidney tissues. Macrophages following lipopolysaccharides (LPS) and adenosine 5′-triphosphate (ATP) stimulation were examined by Western blot, spectrophotometry, and TEM.
Results
Compared with the untreated UUO rats, AKF-PD treatment significantly mitigated the UUO procedure-induced renal fibrosis in rats. AKF-PD treatment decreased mitochondrial dysfunction and IL-Iβ and caspase-1 expression in rat kidney tissues and reduced mitochondrial reactive oxygen species production in activated macrophages. Mechanistically, AKF-PD treatment significantly attenuated the PI3K/AKT/mTOR signaling, increased Beclin-1 and LC3 II expression and autophagosome formation, and ameliorated the mitochondrial damage in renal tissues and activated macrophages.
Conclusion
The results indicated that AKF-PD treatment inhibited renal interstitial fibrosis by regulating the autophagy-mitochondria-NLRP3 inflammasome pathway.</abstract><cop>New York</cop><pub>Springer US</pub><doi>10.1007/s12013-023-01176-7</doi><tpages>9</tpages></addata></record> |
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| subjects | 1-Phosphatidylinositol 3-kinase Adenosine AKT protein Animal tissues Autophagy Biochemistry Biological and Medical Physics Biomedical and Life Sciences Biophysics Biotechnology Caspase-1 Cell Biology Fibrosis Inflammasomes Kidneys Life Sciences Lipopolysaccharides Macrophages Mitochondria Original Paper Pharmacology/Toxicology Reactive oxygen species Spectrophotometry TOR protein |
| title | Fluorofenidone Attenuates Renal Interstitial Fibrosis by Enhancing Autophagy and Retaining Mitochondrial Function |
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