Iguratimod ameliorates rheumatoid arthritis progression through regulating miR-146a mediated IRAK1 expression and TRAF6/JNK1 pathway: an in vivo and in vitro study
Objective This study aimed to evaluate the therapeutic effect of iguratimod and its regulatory role on microRNA (miR-146a) and the downstream genes in treating rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLS) and collagen-induced arthritis (CIA) rat model. Methods RA-FLS was isolated from...
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| Veröffentlicht in: | CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2021-03, Vol.39 (2), p.289-303 |
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| container_title | CLINICAL AND EXPERIMENTAL RHEUMATOLOGY |
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| creator | Kong, R. Gao, J. Ji, L. Peng, Y. Zhang, J. Zhao, D. |
| description | Objective
This study aimed to evaluate the therapeutic effect of iguratimod and its regulatory role on microRNA (miR-146a) and the downstream genes in treating rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLS) and collagen-induced arthritis (CIA) rat model.
Methods
RA-FLS was isolated from knee synovial tissue of an active RA patient. In vitro, the effect of miR-146a mimic/inhibition on RA-FLS functions was investigated. Then the effect of Iguratimod on cell viability, proliferation, apoptosis, migration, invasion, inflammatory cytokines, miR-146a and its downstream gene/pathway in RA-FLS was evaluated. In vivo, the collagen induced arthritis (CIA) rat model was constructed, then the effects of iguratimod, miR-146a inhibition and their combination on treating CIA rat were assessed.
Results
Iguratimod treatment increased miR-146a while decreased cell proliferation, IRAK1 and TRAF6/JNK1 pathway in RA-FLS in a dose-dependent manner. Notably, iguratimod treatment repressed cell proliferation, migration, invasion, TNF-alpha, IL-1 beta, IL-6, IL-17, IRAK1 and TRAF6/JNK1 pathway in RA-FLS, while miR-146a inhibition alleviated the abovementioned effects of Iguratimod on RA-FLS. The in vivo experiments disclosed that iguratimod reduced systemic arthritis score, and decreased TNF-alpha, IL-1 beta, IL-6, IL-17, IRAK1 as well as TRAF6/JNK1 pathway, while enhanced apoptosis in synovial tissue of CIA rat model; and in miR-146a inhibition treated CIA rat model, the effect of iguratimod was diminished.
Conclusion
Iguratimod ameliorates RA progression via regulating miR-146a mediated IRAK1 expression and TRAF6/JNK1 pathway. |
| doi_str_mv | 10.55563/clinexprheumatol/urhbn0 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_2423800961</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2423800961</sourcerecordid><originalsourceid>FETCH-LOGICAL-c381t-ed65177807e4447fa7678709ceeb9d3a95e80e4f1f1acc79baafa3b245a31a573</originalsourceid><addsrcrecordid>eNqNkd9u0zAUxi0EYt3gFZAvkVBWO47thLuq2qAwgVQNaXeRk5wkRold_Gejz8OLYtpuSFxx5ePPv_P52B9CmJJLzrlgy3bSBn7u3AhxVsFOy-jGxpBnaEF5xTJSlXfP0YKwKs9KLu7O0Ln33wnJBRfyJTpjuRB5QekC_doM0amgZ9thNcOkbdqBx4_OOskujE4H7fHO2cGB99oanDQbhxE7GOKUDMyAZ73NaCEUnqHTyaXDm-3qM8V_Bj11KdPh2-3qWiw_fUknOxXGB7V_n3SsDb7X9_aAHOrgLPYhdvtX6EWvJg-vT-sF-nZ9dbv-mN18_bBZr26ylpU0ZNAJTqUsiYSiKGSvpJClJFUL0FQdUxWHkkDR056qtpVVo1SvWJMXXDGquGQX6O3RN73zRwQf6ln7FqZJGbDR13mRs5KQStCElke0ddZ7B329c3pWbl9TUh8iqv-NqD5GlFrfnG6JTfqop8bHTBLw7gg8QGN732owLTxhhBDBGS1ZlSrC_07yP_RahxSVNWsbTWC_Ab6buKg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2423800961</pqid></control><display><type>article</type><title>Iguratimod ameliorates rheumatoid arthritis progression through regulating miR-146a mediated IRAK1 expression and TRAF6/JNK1 pathway: an in vivo and in vitro study</title><source>MEDLINE</source><source>Web of Science - Science Citation Index Expanded - 2021<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /></source><source>Alma/SFX Local Collection</source><creator>Kong, R. ; Gao, J. ; Ji, L. ; Peng, Y. ; Zhang, J. ; Zhao, D.</creator><creatorcontrib>Kong, R. ; Gao, J. ; Ji, L. ; Peng, Y. ; Zhang, J. ; Zhao, D.</creatorcontrib><description>Objective
This study aimed to evaluate the therapeutic effect of iguratimod and its regulatory role on microRNA (miR-146a) and the downstream genes in treating rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLS) and collagen-induced arthritis (CIA) rat model.
Methods
RA-FLS was isolated from knee synovial tissue of an active RA patient. In vitro, the effect of miR-146a mimic/inhibition on RA-FLS functions was investigated. Then the effect of Iguratimod on cell viability, proliferation, apoptosis, migration, invasion, inflammatory cytokines, miR-146a and its downstream gene/pathway in RA-FLS was evaluated. In vivo, the collagen induced arthritis (CIA) rat model was constructed, then the effects of iguratimod, miR-146a inhibition and their combination on treating CIA rat were assessed.
Results
Iguratimod treatment increased miR-146a while decreased cell proliferation, IRAK1 and TRAF6/JNK1 pathway in RA-FLS in a dose-dependent manner. Notably, iguratimod treatment repressed cell proliferation, migration, invasion, TNF-alpha, IL-1 beta, IL-6, IL-17, IRAK1 and TRAF6/JNK1 pathway in RA-FLS, while miR-146a inhibition alleviated the abovementioned effects of Iguratimod on RA-FLS. The in vivo experiments disclosed that iguratimod reduced systemic arthritis score, and decreased TNF-alpha, IL-1 beta, IL-6, IL-17, IRAK1 as well as TRAF6/JNK1 pathway, while enhanced apoptosis in synovial tissue of CIA rat model; and in miR-146a inhibition treated CIA rat model, the effect of iguratimod was diminished.
Conclusion
Iguratimod ameliorates RA progression via regulating miR-146a mediated IRAK1 expression and TRAF6/JNK1 pathway.</description><identifier>ISSN: 0392-856X</identifier><identifier>EISSN: 1593-098X</identifier><identifier>DOI: 10.55563/clinexprheumatol/urhbn0</identifier><identifier>PMID: 32662411</identifier><language>eng</language><publisher>PISA: Clinical & Exper Rheumatology</publisher><subject>Animals ; Arthritis, Rheumatoid - drug therapy ; Cell Proliferation ; Cells, Cultured ; Chromones ; Fibroblasts ; Humans ; Interleukin-1 Receptor-Associated Kinases - genetics ; Life Sciences & Biomedicine ; MicroRNAs - genetics ; Rats ; Rheumatology ; Science & Technology ; Sulfonamides ; Synovial Membrane ; Synoviocytes ; TNF Receptor-Associated Factor 6 - genetics</subject><ispartof>CLINICAL AND EXPERIMENTAL RHEUMATOLOGY, 2021-03, Vol.39 (2), p.289-303</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>8</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000653183900005</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c381t-ed65177807e4447fa7678709ceeb9d3a95e80e4f1f1acc79baafa3b245a31a573</citedby><cites>FETCH-LOGICAL-c381t-ed65177807e4447fa7678709ceeb9d3a95e80e4f1f1acc79baafa3b245a31a573</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,27931,27932,39265</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32662411$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kong, R.</creatorcontrib><creatorcontrib>Gao, J.</creatorcontrib><creatorcontrib>Ji, L.</creatorcontrib><creatorcontrib>Peng, Y.</creatorcontrib><creatorcontrib>Zhang, J.</creatorcontrib><creatorcontrib>Zhao, D.</creatorcontrib><title>Iguratimod ameliorates rheumatoid arthritis progression through regulating miR-146a mediated IRAK1 expression and TRAF6/JNK1 pathway: an in vivo and in vitro study</title><title>CLINICAL AND EXPERIMENTAL RHEUMATOLOGY</title><addtitle>CLIN EXP RHEUMATOL</addtitle><addtitle>Clin Exp Rheumatol</addtitle><description>Objective
This study aimed to evaluate the therapeutic effect of iguratimod and its regulatory role on microRNA (miR-146a) and the downstream genes in treating rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLS) and collagen-induced arthritis (CIA) rat model.
Methods
RA-FLS was isolated from knee synovial tissue of an active RA patient. In vitro, the effect of miR-146a mimic/inhibition on RA-FLS functions was investigated. Then the effect of Iguratimod on cell viability, proliferation, apoptosis, migration, invasion, inflammatory cytokines, miR-146a and its downstream gene/pathway in RA-FLS was evaluated. In vivo, the collagen induced arthritis (CIA) rat model was constructed, then the effects of iguratimod, miR-146a inhibition and their combination on treating CIA rat were assessed.
Results
Iguratimod treatment increased miR-146a while decreased cell proliferation, IRAK1 and TRAF6/JNK1 pathway in RA-FLS in a dose-dependent manner. Notably, iguratimod treatment repressed cell proliferation, migration, invasion, TNF-alpha, IL-1 beta, IL-6, IL-17, IRAK1 and TRAF6/JNK1 pathway in RA-FLS, while miR-146a inhibition alleviated the abovementioned effects of Iguratimod on RA-FLS. The in vivo experiments disclosed that iguratimod reduced systemic arthritis score, and decreased TNF-alpha, IL-1 beta, IL-6, IL-17, IRAK1 as well as TRAF6/JNK1 pathway, while enhanced apoptosis in synovial tissue of CIA rat model; and in miR-146a inhibition treated CIA rat model, the effect of iguratimod was diminished.
Conclusion
Iguratimod ameliorates RA progression via regulating miR-146a mediated IRAK1 expression and TRAF6/JNK1 pathway.</description><subject>Animals</subject><subject>Arthritis, Rheumatoid - drug therapy</subject><subject>Cell Proliferation</subject><subject>Cells, Cultured</subject><subject>Chromones</subject><subject>Fibroblasts</subject><subject>Humans</subject><subject>Interleukin-1 Receptor-Associated Kinases - genetics</subject><subject>Life Sciences & Biomedicine</subject><subject>MicroRNAs - genetics</subject><subject>Rats</subject><subject>Rheumatology</subject><subject>Science & Technology</subject><subject>Sulfonamides</subject><subject>Synovial Membrane</subject><subject>Synoviocytes</subject><subject>TNF Receptor-Associated Factor 6 - genetics</subject><issn>0392-856X</issn><issn>1593-098X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>HGBXW</sourceid><sourceid>EIF</sourceid><recordid>eNqNkd9u0zAUxi0EYt3gFZAvkVBWO47thLuq2qAwgVQNaXeRk5wkRold_Gejz8OLYtpuSFxx5ePPv_P52B9CmJJLzrlgy3bSBn7u3AhxVsFOy-jGxpBnaEF5xTJSlXfP0YKwKs9KLu7O0Ln33wnJBRfyJTpjuRB5QekC_doM0amgZ9thNcOkbdqBx4_OOskujE4H7fHO2cGB99oanDQbhxE7GOKUDMyAZ73NaCEUnqHTyaXDm-3qM8V_Bj11KdPh2-3qWiw_fUknOxXGB7V_n3SsDb7X9_aAHOrgLPYhdvtX6EWvJg-vT-sF-nZ9dbv-mN18_bBZr26ylpU0ZNAJTqUsiYSiKGSvpJClJFUL0FQdUxWHkkDR056qtpVVo1SvWJMXXDGquGQX6O3RN73zRwQf6ln7FqZJGbDR13mRs5KQStCElke0ddZ7B329c3pWbl9TUh8iqv-NqD5GlFrfnG6JTfqop8bHTBLw7gg8QGN732owLTxhhBDBGS1ZlSrC_07yP_RahxSVNWsbTWC_Ab6buKg</recordid><startdate>20210301</startdate><enddate>20210301</enddate><creator>Kong, R.</creator><creator>Gao, J.</creator><creator>Ji, L.</creator><creator>Peng, Y.</creator><creator>Zhang, J.</creator><creator>Zhao, D.</creator><general>Clinical & Exper Rheumatology</general><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</scope><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>7X8</scope></search><sort><creationdate>20210301</creationdate><title>Iguratimod ameliorates rheumatoid arthritis progression through regulating miR-146a mediated IRAK1 expression and TRAF6/JNK1 pathway: an in vivo and in vitro study</title><author>Kong, R. ; Gao, J. ; Ji, L. ; Peng, Y. ; Zhang, J. ; Zhao, D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c381t-ed65177807e4447fa7678709ceeb9d3a95e80e4f1f1acc79baafa3b245a31a573</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Arthritis, Rheumatoid - drug therapy</topic><topic>Cell Proliferation</topic><topic>Cells, Cultured</topic><topic>Chromones</topic><topic>Fibroblasts</topic><topic>Humans</topic><topic>Interleukin-1 Receptor-Associated Kinases - genetics</topic><topic>Life Sciences & Biomedicine</topic><topic>MicroRNAs - genetics</topic><topic>Rats</topic><topic>Rheumatology</topic><topic>Science & Technology</topic><topic>Sulfonamides</topic><topic>Synovial Membrane</topic><topic>Synoviocytes</topic><topic>TNF Receptor-Associated Factor 6 - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kong, R.</creatorcontrib><creatorcontrib>Gao, J.</creatorcontrib><creatorcontrib>Ji, L.</creatorcontrib><creatorcontrib>Peng, Y.</creatorcontrib><creatorcontrib>Zhang, J.</creatorcontrib><creatorcontrib>Zhao, D.</creatorcontrib><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Web of Science - Science Citation Index Expanded - 2021</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>CLINICAL AND EXPERIMENTAL RHEUMATOLOGY</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kong, R.</au><au>Gao, J.</au><au>Ji, L.</au><au>Peng, Y.</au><au>Zhang, J.</au><au>Zhao, D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Iguratimod ameliorates rheumatoid arthritis progression through regulating miR-146a mediated IRAK1 expression and TRAF6/JNK1 pathway: an in vivo and in vitro study</atitle><jtitle>CLINICAL AND EXPERIMENTAL RHEUMATOLOGY</jtitle><stitle>CLIN EXP RHEUMATOL</stitle><addtitle>Clin Exp Rheumatol</addtitle><date>2021-03-01</date><risdate>2021</risdate><volume>39</volume><issue>2</issue><spage>289</spage><epage>303</epage><pages>289-303</pages><issn>0392-856X</issn><eissn>1593-098X</eissn><abstract>Objective
This study aimed to evaluate the therapeutic effect of iguratimod and its regulatory role on microRNA (miR-146a) and the downstream genes in treating rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLS) and collagen-induced arthritis (CIA) rat model.
Methods
RA-FLS was isolated from knee synovial tissue of an active RA patient. In vitro, the effect of miR-146a mimic/inhibition on RA-FLS functions was investigated. Then the effect of Iguratimod on cell viability, proliferation, apoptosis, migration, invasion, inflammatory cytokines, miR-146a and its downstream gene/pathway in RA-FLS was evaluated. In vivo, the collagen induced arthritis (CIA) rat model was constructed, then the effects of iguratimod, miR-146a inhibition and their combination on treating CIA rat were assessed.
Results
Iguratimod treatment increased miR-146a while decreased cell proliferation, IRAK1 and TRAF6/JNK1 pathway in RA-FLS in a dose-dependent manner. Notably, iguratimod treatment repressed cell proliferation, migration, invasion, TNF-alpha, IL-1 beta, IL-6, IL-17, IRAK1 and TRAF6/JNK1 pathway in RA-FLS, while miR-146a inhibition alleviated the abovementioned effects of Iguratimod on RA-FLS. The in vivo experiments disclosed that iguratimod reduced systemic arthritis score, and decreased TNF-alpha, IL-1 beta, IL-6, IL-17, IRAK1 as well as TRAF6/JNK1 pathway, while enhanced apoptosis in synovial tissue of CIA rat model; and in miR-146a inhibition treated CIA rat model, the effect of iguratimod was diminished.
Conclusion
Iguratimod ameliorates RA progression via regulating miR-146a mediated IRAK1 expression and TRAF6/JNK1 pathway.</abstract><cop>PISA</cop><pub>Clinical & Exper Rheumatology</pub><pmid>32662411</pmid><doi>10.55563/clinexprheumatol/urhbn0</doi><tpages>15</tpages></addata></record> |
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| identifier | ISSN: 0392-856X |
| ispartof | CLINICAL AND EXPERIMENTAL RHEUMATOLOGY, 2021-03, Vol.39 (2), p.289-303 |
| issn | 0392-856X 1593-098X |
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| source | MEDLINE; Web of Science - Science Citation Index Expanded - 2021<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" />; Alma/SFX Local Collection |
| subjects | Animals Arthritis, Rheumatoid - drug therapy Cell Proliferation Cells, Cultured Chromones Fibroblasts Humans Interleukin-1 Receptor-Associated Kinases - genetics Life Sciences & Biomedicine MicroRNAs - genetics Rats Rheumatology Science & Technology Sulfonamides Synovial Membrane Synoviocytes TNF Receptor-Associated Factor 6 - genetics |
| title | Iguratimod ameliorates rheumatoid arthritis progression through regulating miR-146a mediated IRAK1 expression and TRAF6/JNK1 pathway: an in vivo and in vitro study |
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