The Anti-fibrotic Effects of Heat-Killed Akkermansia muciniphila MucT on Liver Fibrosis Markers and Activation of Hepatic Stellate Cells
Hepatic stellate cell (HSC) activation is a key phenomenon in development of liver fibrosis. Recently, Akkermansia muciniphila has been introduced as a next-generation microbe residing in the mucosal layer of the human gut. Due to the probable risks associated with the use of live probiotics, the te...
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| Veröffentlicht in: | Probiotics and antimicrobial proteins 2021-06, Vol.13 (3), p.776-787 |
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| creator | Keshavarz Azizi Raftar, Shahrbanoo Abdollahiyan, Sara Azimirad, Masoumeh Yadegar, Abbas Vaziri, Farzam Moshiri, Arfa Siadat, Seyed Davar Zali, Mohammad Reza |
| description | Hepatic stellate cell (HSC) activation is a key phenomenon in development of liver fibrosis. Recently,
Akkermansia muciniphila
has been introduced as a next-generation microbe residing in the mucosal layer of the human gut. Due to the probable risks associated with the use of live probiotics, the tendency to use heat-killed bacteria has been raised. Herein, we investigated the potential anti-fibrotic effects of heat-killed
A. muciniphila
MucT on activation of HSCs. The human LX-2 cells were stimulated by various concentrations of LPS to evaluate the optimal concentration for HSC activation. Cell viability of LX-2 cells treated with LPS and heat-killed
A. muciniphila
MucT was measured by MTT assay. Scanning electron microscopy was used to analyze the morphology of heat-killed bacteria. Quiescent and LPS-stimulated LX-2 cells were coinfected with heat-killed
A. muciniphila
MucT. The gene expression of α-SMA, TIMP, Col1, TGF-β, TLR4, and PPARγ was analyzed using quantitative real-time PCR. Our results showed that LPS treatment led to a significant increase in fibrosis markers in a concentration-independent manner (
P
|
| doi_str_mv | 10.1007/s12602-020-09733-9 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2477263447</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2477263447</sourcerecordid><originalsourceid>FETCH-LOGICAL-c375t-a80aa2ec2f75f5d56c7d0d33a0fb2b0cc1d701176e9a821cf944cf7b0e85785c3</originalsourceid><addsrcrecordid>eNp9kctOHDEQRa2IKLzyAywiS2yycVJ-tN29HI14RBnEgmFtud02GPoxsd1I-QM-Gw9DiJRFVlVSnXurShehEwrfKID6niiTwAgwINAozknzAR3QWipCORV77z3IfXSY0gOAlJzBJ7TPueC8btQBel7fO7wYcyA-tHHKweIz753NCU8eXzqTyc_Q967Di8dHFwczpmDwMNswhs196A2-mu0aTyNehScX8fnWJYWEr0wsfMJmLFKbw5PJoVCvphuz3XOTXd-b7PCy1HSMPnrTJ_f5rR6h2_Oz9fKSrK4vfiwXK2K5qjIxNRjDnGVeVb7qKmlVBx3nBnzLWrCWdgooVdI1pmbU-kYI61ULrq5UXVl-hL7ufDdx-jW7lPUQkt1eMrppTpoJpZjkQqiCnv6DPkxzHMt1mlUChKxBQaHYjrLl8RSd15sYBhN_awp6m5Pe5aRLTvo1J90U0Zc367kdXPcu-RNMAfgOSGU03rn4d_d_bF8A_y2eSA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2540468070</pqid></control><display><type>article</type><title>The Anti-fibrotic Effects of Heat-Killed Akkermansia muciniphila MucT on Liver Fibrosis Markers and Activation of Hepatic Stellate Cells</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Keshavarz Azizi Raftar, Shahrbanoo ; Abdollahiyan, Sara ; Azimirad, Masoumeh ; Yadegar, Abbas ; Vaziri, Farzam ; Moshiri, Arfa ; Siadat, Seyed Davar ; Zali, Mohammad Reza</creator><creatorcontrib>Keshavarz Azizi Raftar, Shahrbanoo ; Abdollahiyan, Sara ; Azimirad, Masoumeh ; Yadegar, Abbas ; Vaziri, Farzam ; Moshiri, Arfa ; Siadat, Seyed Davar ; Zali, Mohammad Reza</creatorcontrib><description>Hepatic stellate cell (HSC) activation is a key phenomenon in development of liver fibrosis. Recently,
Akkermansia muciniphila
has been introduced as a next-generation microbe residing in the mucosal layer of the human gut. Due to the probable risks associated with the use of live probiotics, the tendency to use heat-killed bacteria has been raised. Herein, we investigated the potential anti-fibrotic effects of heat-killed
A. muciniphila
MucT on activation of HSCs. The human LX-2 cells were stimulated by various concentrations of LPS to evaluate the optimal concentration for HSC activation. Cell viability of LX-2 cells treated with LPS and heat-killed
A. muciniphila
MucT was measured by MTT assay. Scanning electron microscopy was used to analyze the morphology of heat-killed bacteria. Quiescent and LPS-stimulated LX-2 cells were coinfected with heat-killed
A. muciniphila
MucT. The gene expression of α-SMA, TIMP, Col1, TGF-β, TLR4, and PPARγ was analyzed using quantitative real-time PCR. Our results showed that LPS treatment led to a significant increase in fibrosis markers in a concentration-independent manner (
P
< 0.0001), and significantly downregulated the expression of PPARγ (
P
< 0.0001). The heat-killed
A. muciniphila
MucT could significantly modulate the expression of fibrosis markers particularly in MOI 10 (
P
< 0.0001), and reversed the HSC activation in LPS-stimulated LX-2 cells. In conclusion, we demonstrated that heat-killed
A. muciniphila
MucT was safe and capable to ameliorate LPS-induced HSC activation through modulation of fibrosis markers. Further in vivo studies are required to validate the anti-fibrotic properties of heat-killed
A. muciniphila
MucT.</description><identifier>ISSN: 1867-1306</identifier><identifier>EISSN: 1867-1314</identifier><identifier>DOI: 10.1007/s12602-020-09733-9</identifier><identifier>PMID: 33433897</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Akkermansia ; Akkermansia muciniphila ; Applied Microbiology ; Bacteria ; Cell activation ; Cell Line ; Cell viability ; Chemistry ; Chemistry and Materials Science ; Chemistry/Food Science ; Cytology ; Fibrosis ; Gene expression ; Heat ; Hepatic Stellate Cells ; Hot Temperature ; Humans ; Lipopolysaccharides ; Liver ; Liver Cirrhosis - therapy ; Microbiology ; Mucosa ; Nutrition ; Probiotics ; Protein Science ; Scanning electron microscopy ; Stellate cells ; TLR4 protein ; Toll-like receptors</subject><ispartof>Probiotics and antimicrobial proteins, 2021-06, Vol.13 (3), p.776-787</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature 2021</rights><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-a80aa2ec2f75f5d56c7d0d33a0fb2b0cc1d701176e9a821cf944cf7b0e85785c3</citedby><cites>FETCH-LOGICAL-c375t-a80aa2ec2f75f5d56c7d0d33a0fb2b0cc1d701176e9a821cf944cf7b0e85785c3</cites><orcidid>0000-0002-2135-7581 ; 0000-0002-4492-6716</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12602-020-09733-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12602-020-09733-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33433897$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Keshavarz Azizi Raftar, Shahrbanoo</creatorcontrib><creatorcontrib>Abdollahiyan, Sara</creatorcontrib><creatorcontrib>Azimirad, Masoumeh</creatorcontrib><creatorcontrib>Yadegar, Abbas</creatorcontrib><creatorcontrib>Vaziri, Farzam</creatorcontrib><creatorcontrib>Moshiri, Arfa</creatorcontrib><creatorcontrib>Siadat, Seyed Davar</creatorcontrib><creatorcontrib>Zali, Mohammad Reza</creatorcontrib><title>The Anti-fibrotic Effects of Heat-Killed Akkermansia muciniphila MucT on Liver Fibrosis Markers and Activation of Hepatic Stellate Cells</title><title>Probiotics and antimicrobial proteins</title><addtitle>Probiotics & Antimicro. Prot</addtitle><addtitle>Probiotics Antimicrob Proteins</addtitle><description>Hepatic stellate cell (HSC) activation is a key phenomenon in development of liver fibrosis. Recently,
Akkermansia muciniphila
has been introduced as a next-generation microbe residing in the mucosal layer of the human gut. Due to the probable risks associated with the use of live probiotics, the tendency to use heat-killed bacteria has been raised. Herein, we investigated the potential anti-fibrotic effects of heat-killed
A. muciniphila
MucT on activation of HSCs. The human LX-2 cells were stimulated by various concentrations of LPS to evaluate the optimal concentration for HSC activation. Cell viability of LX-2 cells treated with LPS and heat-killed
A. muciniphila
MucT was measured by MTT assay. Scanning electron microscopy was used to analyze the morphology of heat-killed bacteria. Quiescent and LPS-stimulated LX-2 cells were coinfected with heat-killed
A. muciniphila
MucT. The gene expression of α-SMA, TIMP, Col1, TGF-β, TLR4, and PPARγ was analyzed using quantitative real-time PCR. Our results showed that LPS treatment led to a significant increase in fibrosis markers in a concentration-independent manner (
P
< 0.0001), and significantly downregulated the expression of PPARγ (
P
< 0.0001). The heat-killed
A. muciniphila
MucT could significantly modulate the expression of fibrosis markers particularly in MOI 10 (
P
< 0.0001), and reversed the HSC activation in LPS-stimulated LX-2 cells. In conclusion, we demonstrated that heat-killed
A. muciniphila
MucT was safe and capable to ameliorate LPS-induced HSC activation through modulation of fibrosis markers. Further in vivo studies are required to validate the anti-fibrotic properties of heat-killed
A. muciniphila
MucT.</description><subject>Akkermansia</subject><subject>Akkermansia muciniphila</subject><subject>Applied Microbiology</subject><subject>Bacteria</subject><subject>Cell activation</subject><subject>Cell Line</subject><subject>Cell viability</subject><subject>Chemistry</subject><subject>Chemistry and Materials Science</subject><subject>Chemistry/Food Science</subject><subject>Cytology</subject><subject>Fibrosis</subject><subject>Gene expression</subject><subject>Heat</subject><subject>Hepatic Stellate Cells</subject><subject>Hot Temperature</subject><subject>Humans</subject><subject>Lipopolysaccharides</subject><subject>Liver</subject><subject>Liver Cirrhosis - therapy</subject><subject>Microbiology</subject><subject>Mucosa</subject><subject>Nutrition</subject><subject>Probiotics</subject><subject>Protein Science</subject><subject>Scanning electron microscopy</subject><subject>Stellate cells</subject><subject>TLR4 protein</subject><subject>Toll-like receptors</subject><issn>1867-1306</issn><issn>1867-1314</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kctOHDEQRa2IKLzyAywiS2yycVJ-tN29HI14RBnEgmFtud02GPoxsd1I-QM-Gw9DiJRFVlVSnXurShehEwrfKID6niiTwAgwINAozknzAR3QWipCORV77z3IfXSY0gOAlJzBJ7TPueC8btQBel7fO7wYcyA-tHHKweIz753NCU8eXzqTyc_Q967Di8dHFwczpmDwMNswhs196A2-mu0aTyNehScX8fnWJYWEr0wsfMJmLFKbw5PJoVCvphuz3XOTXd-b7PCy1HSMPnrTJ_f5rR6h2_Oz9fKSrK4vfiwXK2K5qjIxNRjDnGVeVb7qKmlVBx3nBnzLWrCWdgooVdI1pmbU-kYI61ULrq5UXVl-hL7ufDdx-jW7lPUQkt1eMrppTpoJpZjkQqiCnv6DPkxzHMt1mlUChKxBQaHYjrLl8RSd15sYBhN_awp6m5Pe5aRLTvo1J90U0Zc367kdXPcu-RNMAfgOSGU03rn4d_d_bF8A_y2eSA</recordid><startdate>20210601</startdate><enddate>20210601</enddate><creator>Keshavarz Azizi Raftar, Shahrbanoo</creator><creator>Abdollahiyan, Sara</creator><creator>Azimirad, Masoumeh</creator><creator>Yadegar, Abbas</creator><creator>Vaziri, Farzam</creator><creator>Moshiri, Arfa</creator><creator>Siadat, Seyed Davar</creator><creator>Zali, Mohammad Reza</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FE</scope><scope>8FH</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-2135-7581</orcidid><orcidid>https://orcid.org/0000-0002-4492-6716</orcidid></search><sort><creationdate>20210601</creationdate><title>The Anti-fibrotic Effects of Heat-Killed Akkermansia muciniphila MucT on Liver Fibrosis Markers and Activation of Hepatic Stellate Cells</title><author>Keshavarz Azizi Raftar, Shahrbanoo ; Abdollahiyan, Sara ; Azimirad, Masoumeh ; Yadegar, Abbas ; Vaziri, Farzam ; Moshiri, Arfa ; Siadat, Seyed Davar ; Zali, Mohammad Reza</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-a80aa2ec2f75f5d56c7d0d33a0fb2b0cc1d701176e9a821cf944cf7b0e85785c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Akkermansia</topic><topic>Akkermansia muciniphila</topic><topic>Applied Microbiology</topic><topic>Bacteria</topic><topic>Cell activation</topic><topic>Cell Line</topic><topic>Cell viability</topic><topic>Chemistry</topic><topic>Chemistry and Materials Science</topic><topic>Chemistry/Food Science</topic><topic>Cytology</topic><topic>Fibrosis</topic><topic>Gene expression</topic><topic>Heat</topic><topic>Hepatic Stellate Cells</topic><topic>Hot Temperature</topic><topic>Humans</topic><topic>Lipopolysaccharides</topic><topic>Liver</topic><topic>Liver Cirrhosis - therapy</topic><topic>Microbiology</topic><topic>Mucosa</topic><topic>Nutrition</topic><topic>Probiotics</topic><topic>Protein Science</topic><topic>Scanning electron microscopy</topic><topic>Stellate cells</topic><topic>TLR4 protein</topic><topic>Toll-like receptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Keshavarz Azizi Raftar, Shahrbanoo</creatorcontrib><creatorcontrib>Abdollahiyan, Sara</creatorcontrib><creatorcontrib>Azimirad, Masoumeh</creatorcontrib><creatorcontrib>Yadegar, Abbas</creatorcontrib><creatorcontrib>Vaziri, Farzam</creatorcontrib><creatorcontrib>Moshiri, Arfa</creatorcontrib><creatorcontrib>Siadat, Seyed Davar</creatorcontrib><creatorcontrib>Zali, Mohammad Reza</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</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>MEDLINE - Academic</collection><jtitle>Probiotics and antimicrobial proteins</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Keshavarz Azizi Raftar, Shahrbanoo</au><au>Abdollahiyan, Sara</au><au>Azimirad, Masoumeh</au><au>Yadegar, Abbas</au><au>Vaziri, Farzam</au><au>Moshiri, Arfa</au><au>Siadat, Seyed Davar</au><au>Zali, Mohammad Reza</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Anti-fibrotic Effects of Heat-Killed Akkermansia muciniphila MucT on Liver Fibrosis Markers and Activation of Hepatic Stellate Cells</atitle><jtitle>Probiotics and antimicrobial proteins</jtitle><stitle>Probiotics & Antimicro. Prot</stitle><addtitle>Probiotics Antimicrob Proteins</addtitle><date>2021-06-01</date><risdate>2021</risdate><volume>13</volume><issue>3</issue><spage>776</spage><epage>787</epage><pages>776-787</pages><issn>1867-1306</issn><eissn>1867-1314</eissn><abstract>Hepatic stellate cell (HSC) activation is a key phenomenon in development of liver fibrosis. Recently,
Akkermansia muciniphila
has been introduced as a next-generation microbe residing in the mucosal layer of the human gut. Due to the probable risks associated with the use of live probiotics, the tendency to use heat-killed bacteria has been raised. Herein, we investigated the potential anti-fibrotic effects of heat-killed
A. muciniphila
MucT on activation of HSCs. The human LX-2 cells were stimulated by various concentrations of LPS to evaluate the optimal concentration for HSC activation. Cell viability of LX-2 cells treated with LPS and heat-killed
A. muciniphila
MucT was measured by MTT assay. Scanning electron microscopy was used to analyze the morphology of heat-killed bacteria. Quiescent and LPS-stimulated LX-2 cells were coinfected with heat-killed
A. muciniphila
MucT. The gene expression of α-SMA, TIMP, Col1, TGF-β, TLR4, and PPARγ was analyzed using quantitative real-time PCR. Our results showed that LPS treatment led to a significant increase in fibrosis markers in a concentration-independent manner (
P
< 0.0001), and significantly downregulated the expression of PPARγ (
P
< 0.0001). The heat-killed
A. muciniphila
MucT could significantly modulate the expression of fibrosis markers particularly in MOI 10 (
P
< 0.0001), and reversed the HSC activation in LPS-stimulated LX-2 cells. In conclusion, we demonstrated that heat-killed
A. muciniphila
MucT was safe and capable to ameliorate LPS-induced HSC activation through modulation of fibrosis markers. Further in vivo studies are required to validate the anti-fibrotic properties of heat-killed
A. muciniphila
MucT.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>33433897</pmid><doi>10.1007/s12602-020-09733-9</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-2135-7581</orcidid><orcidid>https://orcid.org/0000-0002-4492-6716</orcidid></addata></record> |
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| ispartof | Probiotics and antimicrobial proteins, 2021-06, Vol.13 (3), p.776-787 |
| issn | 1867-1306 1867-1314 |
| language | eng |
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| subjects | Akkermansia Akkermansia muciniphila Applied Microbiology Bacteria Cell activation Cell Line Cell viability Chemistry Chemistry and Materials Science Chemistry/Food Science Cytology Fibrosis Gene expression Heat Hepatic Stellate Cells Hot Temperature Humans Lipopolysaccharides Liver Liver Cirrhosis - therapy Microbiology Mucosa Nutrition Probiotics Protein Science Scanning electron microscopy Stellate cells TLR4 protein Toll-like receptors |
| title | The Anti-fibrotic Effects of Heat-Killed Akkermansia muciniphila MucT on Liver Fibrosis Markers and Activation of Hepatic Stellate Cells |
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