Mangiferin prevents hepatocyte epithelial‐mesenchymal transition in liver fibrosis via targeting HSP27‐mediated JAK2/STAT3 and TGF‐β1/Smad pathway

Hepatocytes has been confirmed to undergo EMT and can be converted into myofibroblasts during hepatic fibrogenesis. However, the mechanism of hepatocyte EMT regulation in hepatic fibrosis, particularly through HSP27 (human homologue of rodent HSP25), remains unclear. Mangiferin (MAN), a compound ext...

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Veröffentlicht in:Phytotherapy research 2022-11, Vol.36 (11), p.4167-4182
Hauptverfasser: Zhang, Xiao‐ling, Zhang, Xiao‐yan, Ge, Xiao‐qun, Liu, Ming‐xuan
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container_title Phytotherapy research
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creator Zhang, Xiao‐ling
Zhang, Xiao‐yan
Ge, Xiao‐qun
Liu, Ming‐xuan
description Hepatocytes has been confirmed to undergo EMT and can be converted into myofibroblasts during hepatic fibrogenesis. However, the mechanism of hepatocyte EMT regulation in hepatic fibrosis, particularly through HSP27 (human homologue of rodent HSP25), remains unclear. Mangiferin (MAN), a compound extracted from Mangifera indica L, has been reported to attenuate liver injury. This study aimed to investigate the mechanisms underlying HSP27 inhibition and the anti‐fibrotic effect of MAN in liver fibrosis. Our results revealed that the expression of HSP27 was remarkably increased in the liver tissues of patients with liver cirrhosis and CCl4‐induced fibrotic rats. However, HSP27 shRNA treatment significantly alleviated fibrosis. Furthermore, MAN was found to inhibit CCl4‐ and TGF‐β1‐induced liver fibrosis and reduced hepatocyte EMT. More importantly, MAN decreased HSP27 expression to suppress the JAK2/STAT3 pathway, and subsequently blocked TGF‐β1/Smad signaling, which were consistent with its protection against CCl4‐induced EMT and liver fibrosis. Together, these results suggest that HSP27 may play a crucial role in hepatocyte EMT and liver fibrosis by activating JAK2/STAT3 signaling and TGF‐β1/Smad pathway. The suppression of HSP27 expression by MAN may be a novel strategy for attenuating the hepatocyte EMT in liver fibrosis.
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However, the mechanism of hepatocyte EMT regulation in hepatic fibrosis, particularly through HSP27 (human homologue of rodent HSP25), remains unclear. Mangiferin (MAN), a compound extracted from Mangifera indica L, has been reported to attenuate liver injury. This study aimed to investigate the mechanisms underlying HSP27 inhibition and the anti‐fibrotic effect of MAN in liver fibrosis. Our results revealed that the expression of HSP27 was remarkably increased in the liver tissues of patients with liver cirrhosis and CCl4‐induced fibrotic rats. However, HSP27 shRNA treatment significantly alleviated fibrosis. Furthermore, MAN was found to inhibit CCl4‐ and TGF‐β1‐induced liver fibrosis and reduced hepatocyte EMT. More importantly, MAN decreased HSP27 expression to suppress the JAK2/STAT3 pathway, and subsequently blocked TGF‐β1/Smad signaling, which were consistent with its protection against CCl4‐induced EMT and liver fibrosis. Together, these results suggest that HSP27 may play a crucial role in hepatocyte EMT and liver fibrosis by activating JAK2/STAT3 signaling and TGF‐β1/Smad pathway. The suppression of HSP27 expression by MAN may be a novel strategy for attenuating the hepatocyte EMT in liver fibrosis.</description><identifier>ISSN: 0951-418X</identifier><identifier>EISSN: 1099-1573</identifier><identifier>DOI: 10.1002/ptr.7549</identifier><language>eng</language><publisher>Chichester, UK: John Wiley &amp; Sons, Ltd</publisher><subject>Carbon tetrachloride ; Cirrhosis ; EMT ; Fibrosis ; Hepatocytes ; Hsp25 protein ; HSP27 ; Hsp27 protein ; JAK2/STAT3 signaling ; Janus kinase 2 ; Liver ; Liver cirrhosis ; liver fibrosis ; Mangiferin ; Mesenchyme ; Signal transduction ; Signaling ; Smad protein ; Stat3 protein ; TGF‐β1/Smad pathway</subject><ispartof>Phytotherapy research, 2022-11, Vol.36 (11), p.4167-4182</ispartof><rights>2022 John Wiley &amp; Sons Ltd.</rights><rights>2022 John Wiley &amp; Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3269-95d408742cebeacf66a91535f91632faf46f87b339672a3ee9fd76e27d5244573</citedby><cites>FETCH-LOGICAL-c3269-95d408742cebeacf66a91535f91632faf46f87b339672a3ee9fd76e27d5244573</cites><orcidid>0000-0002-0723-143X ; 0000-0003-1157-0976</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%2Fptr.7549$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fptr.7549$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids></links><search><creatorcontrib>Zhang, Xiao‐ling</creatorcontrib><creatorcontrib>Zhang, Xiao‐yan</creatorcontrib><creatorcontrib>Ge, Xiao‐qun</creatorcontrib><creatorcontrib>Liu, Ming‐xuan</creatorcontrib><title>Mangiferin prevents hepatocyte epithelial‐mesenchymal transition in liver fibrosis via targeting HSP27‐mediated JAK2/STAT3 and TGF‐β1/Smad pathway</title><title>Phytotherapy research</title><description>Hepatocytes has been confirmed to undergo EMT and can be converted into myofibroblasts during hepatic fibrogenesis. However, the mechanism of hepatocyte EMT regulation in hepatic fibrosis, particularly through HSP27 (human homologue of rodent HSP25), remains unclear. Mangiferin (MAN), a compound extracted from Mangifera indica L, has been reported to attenuate liver injury. This study aimed to investigate the mechanisms underlying HSP27 inhibition and the anti‐fibrotic effect of MAN in liver fibrosis. Our results revealed that the expression of HSP27 was remarkably increased in the liver tissues of patients with liver cirrhosis and CCl4‐induced fibrotic rats. However, HSP27 shRNA treatment significantly alleviated fibrosis. Furthermore, MAN was found to inhibit CCl4‐ and TGF‐β1‐induced liver fibrosis and reduced hepatocyte EMT. More importantly, MAN decreased HSP27 expression to suppress the JAK2/STAT3 pathway, and subsequently blocked TGF‐β1/Smad signaling, which were consistent with its protection against CCl4‐induced EMT and liver fibrosis. Together, these results suggest that HSP27 may play a crucial role in hepatocyte EMT and liver fibrosis by activating JAK2/STAT3 signaling and TGF‐β1/Smad pathway. The suppression of HSP27 expression by MAN may be a novel strategy for attenuating the hepatocyte EMT in liver fibrosis.</description><subject>Carbon tetrachloride</subject><subject>Cirrhosis</subject><subject>EMT</subject><subject>Fibrosis</subject><subject>Hepatocytes</subject><subject>Hsp25 protein</subject><subject>HSP27</subject><subject>Hsp27 protein</subject><subject>JAK2/STAT3 signaling</subject><subject>Janus kinase 2</subject><subject>Liver</subject><subject>Liver cirrhosis</subject><subject>liver fibrosis</subject><subject>Mangiferin</subject><subject>Mesenchyme</subject><subject>Signal transduction</subject><subject>Signaling</subject><subject>Smad protein</subject><subject>Stat3 protein</subject><subject>TGF‐β1/Smad pathway</subject><issn>0951-418X</issn><issn>1099-1573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp1kc1u1DAUhS0EEkNB4hEssWGTju04drwcVfSPIiomSOwsT3I94ypxgu2ZKjsegW1fgwfhIXgS3BYJCYnVXdzvnHN1D0KvKTmmhLDllMKxrLh6ghaUKFXQSpZP0YKoihac1l-eoxcx3hBCFCN8ge4-GL91FoLzeApwAJ8i3sFk0tjOCTBMLu2gd6b_9e37ABF8u5sH0-MUjI8uudHjLO3dAQK2bhPG6CI-OIOTCVtIzm_x-fqayQd550yCDl-u3rPlulk1JTa-w83Zad7-_EGX68F0OGfvbs38Ej2zpo_w6s88Qp9P3zUn58XVx7OLk9VV0ZZMqEJVHSe15KyFDZjWCmEUrcrKKipKZo3lwtZyU5ZKSGZKAGU7KYDJrmKc5-ccobePvlMYv-4hJj242ELfGw_jPmomak5UTTjP6Jt_0JtxH3y-TjNZihxBBPlr2OZnxABWT8ENJsyaEn3fkc4d6fuOMlo8oreuh_m_nL5uPj3wvwEzaZdI</recordid><startdate>202211</startdate><enddate>202211</enddate><creator>Zhang, Xiao‐ling</creator><creator>Zhang, Xiao‐yan</creator><creator>Ge, Xiao‐qun</creator><creator>Liu, Ming‐xuan</creator><general>John Wiley &amp; Sons, Ltd</general><general>Wiley Subscription Services, Inc</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0723-143X</orcidid><orcidid>https://orcid.org/0000-0003-1157-0976</orcidid></search><sort><creationdate>202211</creationdate><title>Mangiferin prevents hepatocyte epithelial‐mesenchymal transition in liver fibrosis via targeting HSP27‐mediated JAK2/STAT3 and TGF‐β1/Smad pathway</title><author>Zhang, Xiao‐ling ; Zhang, Xiao‐yan ; Ge, Xiao‐qun ; Liu, Ming‐xuan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3269-95d408742cebeacf66a91535f91632faf46f87b339672a3ee9fd76e27d5244573</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Carbon tetrachloride</topic><topic>Cirrhosis</topic><topic>EMT</topic><topic>Fibrosis</topic><topic>Hepatocytes</topic><topic>Hsp25 protein</topic><topic>HSP27</topic><topic>Hsp27 protein</topic><topic>JAK2/STAT3 signaling</topic><topic>Janus kinase 2</topic><topic>Liver</topic><topic>Liver cirrhosis</topic><topic>liver fibrosis</topic><topic>Mangiferin</topic><topic>Mesenchyme</topic><topic>Signal transduction</topic><topic>Signaling</topic><topic>Smad protein</topic><topic>Stat3 protein</topic><topic>TGF‐β1/Smad pathway</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Xiao‐ling</creatorcontrib><creatorcontrib>Zhang, Xiao‐yan</creatorcontrib><creatorcontrib>Ge, Xiao‐qun</creatorcontrib><creatorcontrib>Liu, Ming‐xuan</creatorcontrib><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Phytotherapy research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Xiao‐ling</au><au>Zhang, Xiao‐yan</au><au>Ge, Xiao‐qun</au><au>Liu, Ming‐xuan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mangiferin prevents hepatocyte epithelial‐mesenchymal transition in liver fibrosis via targeting HSP27‐mediated JAK2/STAT3 and TGF‐β1/Smad pathway</atitle><jtitle>Phytotherapy research</jtitle><date>2022-11</date><risdate>2022</risdate><volume>36</volume><issue>11</issue><spage>4167</spage><epage>4182</epage><pages>4167-4182</pages><issn>0951-418X</issn><eissn>1099-1573</eissn><abstract>Hepatocytes has been confirmed to undergo EMT and can be converted into myofibroblasts during hepatic fibrogenesis. 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Together, these results suggest that HSP27 may play a crucial role in hepatocyte EMT and liver fibrosis by activating JAK2/STAT3 signaling and TGF‐β1/Smad pathway. The suppression of HSP27 expression by MAN may be a novel strategy for attenuating the hepatocyte EMT in liver fibrosis.</abstract><cop>Chichester, UK</cop><pub>John Wiley &amp; Sons, Ltd</pub><doi>10.1002/ptr.7549</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-0723-143X</orcidid><orcidid>https://orcid.org/0000-0003-1157-0976</orcidid></addata></record>
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subjects Carbon tetrachloride
Cirrhosis
EMT
Fibrosis
Hepatocytes
Hsp25 protein
HSP27
Hsp27 protein
JAK2/STAT3 signaling
Janus kinase 2
Liver
Liver cirrhosis
liver fibrosis
Mangiferin
Mesenchyme
Signal transduction
Signaling
Smad protein
Stat3 protein
TGF‐β1/Smad pathway
title Mangiferin prevents hepatocyte epithelial‐mesenchymal transition in liver fibrosis via targeting HSP27‐mediated JAK2/STAT3 and TGF‐β1/Smad pathway
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