FTO-mediated RNA m 6 A methylation regulates synovial aggression and inflammation in rheumatoid arthritis
Fibroblast-like synoviocytes (FLS) plays an important role in synovial inflammation and joint damage in rheumatoid arthritis (RA). As the most abundant mRNA modification, N6-methyladenosine (m A) is involved in the development of various diseases; however, its role in RA remains to be defined. In th...
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| Veröffentlicht in: | Biochimica et biophysica acta. Molecular basis of disease 2024-10, Vol.1870 (7), p.167341 |
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| container_title | Biochimica et biophysica acta. Molecular basis of disease |
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| creator | Li, Ruiru Kuang, Yu Niu, Yuanyuan Zhang, Shuoyang Chen, Simin Su, Fan Wang, Jingnan Lin, Shuibin Liu, Di Shen, Chuyu Liang, Liuqin Zheng, Song Guo Jie, Ligang Xiao, Youjun Xu, Hanshi |
| description | Fibroblast-like synoviocytes (FLS) plays an important role in synovial inflammation and joint damage in rheumatoid arthritis (RA). As the most abundant mRNA modification, N6-methyladenosine (m
A) is involved in the development of various diseases; however, its role in RA remains to be defined. In this study, we reported the elevated expression of the m
A demethylase fat mass and obesity-associated protein (FTO) in FLS and synovium from RA patients. Functionally, FTO knockdown or treatment with FB23-2, an inhibitor of the mRNA m
A demethylase FTO, inhibited the migration, invasion and inflammatory response of RA FLS, however, FTO-overexpressed RA FLS exhibited increased migration, invasion and inflammatory response. We further demonstrated that FTO promoted ADAMTS15 mRNA stability in an m
A-IGF2BP1 dependent manner. Notably, the severity of arthritis was significantly reduced in CIA mice with FB23-2 administration or CIA rats with intra-articular injection of FTO shRNA. Our results illustrate the contribution of FTO-mediated m
A modification to joint damage and inflammation in RA and suggest that FTO might be a potential therapeutic target in RA. |
| format | Article |
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A) is involved in the development of various diseases; however, its role in RA remains to be defined. In this study, we reported the elevated expression of the m
A demethylase fat mass and obesity-associated protein (FTO) in FLS and synovium from RA patients. Functionally, FTO knockdown or treatment with FB23-2, an inhibitor of the mRNA m
A demethylase FTO, inhibited the migration, invasion and inflammatory response of RA FLS, however, FTO-overexpressed RA FLS exhibited increased migration, invasion and inflammatory response. We further demonstrated that FTO promoted ADAMTS15 mRNA stability in an m
A-IGF2BP1 dependent manner. Notably, the severity of arthritis was significantly reduced in CIA mice with FB23-2 administration or CIA rats with intra-articular injection of FTO shRNA. Our results illustrate the contribution of FTO-mediated m
A modification to joint damage and inflammation in RA and suggest that FTO might be a potential therapeutic target in RA.</description><identifier>EISSN: 1879-260X</identifier><identifier>PMID: 39025373</identifier><language>eng</language><publisher>Netherlands</publisher><subject>Adenosine - analogs & derivatives ; Adenosine - metabolism ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO - genetics ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO - metabolism ; Animals ; Arthritis, Experimental - genetics ; Arthritis, Experimental - metabolism ; Arthritis, Experimental - pathology ; Arthritis, Rheumatoid - genetics ; Arthritis, Rheumatoid - metabolism ; Arthritis, Rheumatoid - pathology ; Female ; Humans ; Inflammation - genetics ; Inflammation - metabolism ; Inflammation - pathology ; Male ; Methylation ; Mice ; Rats ; RNA Methylation ; RNA Stability ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Synovial Membrane - metabolism ; Synovial Membrane - pathology ; Synoviocytes - metabolism ; Synoviocytes - pathology</subject><ispartof>Biochimica et biophysica acta. Molecular basis of disease, 2024-10, Vol.1870 (7), p.167341</ispartof><rights>Copyright © 2024 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39025373$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Ruiru</creatorcontrib><creatorcontrib>Kuang, Yu</creatorcontrib><creatorcontrib>Niu, Yuanyuan</creatorcontrib><creatorcontrib>Zhang, Shuoyang</creatorcontrib><creatorcontrib>Chen, Simin</creatorcontrib><creatorcontrib>Su, Fan</creatorcontrib><creatorcontrib>Wang, Jingnan</creatorcontrib><creatorcontrib>Lin, Shuibin</creatorcontrib><creatorcontrib>Liu, Di</creatorcontrib><creatorcontrib>Shen, Chuyu</creatorcontrib><creatorcontrib>Liang, Liuqin</creatorcontrib><creatorcontrib>Zheng, Song Guo</creatorcontrib><creatorcontrib>Jie, Ligang</creatorcontrib><creatorcontrib>Xiao, Youjun</creatorcontrib><creatorcontrib>Xu, Hanshi</creatorcontrib><title>FTO-mediated RNA m 6 A methylation regulates synovial aggression and inflammation in rheumatoid arthritis</title><title>Biochimica et biophysica acta. Molecular basis of disease</title><addtitle>Biochim Biophys Acta Mol Basis Dis</addtitle><description>Fibroblast-like synoviocytes (FLS) plays an important role in synovial inflammation and joint damage in rheumatoid arthritis (RA). As the most abundant mRNA modification, N6-methyladenosine (m
A) is involved in the development of various diseases; however, its role in RA remains to be defined. In this study, we reported the elevated expression of the m
A demethylase fat mass and obesity-associated protein (FTO) in FLS and synovium from RA patients. Functionally, FTO knockdown or treatment with FB23-2, an inhibitor of the mRNA m
A demethylase FTO, inhibited the migration, invasion and inflammatory response of RA FLS, however, FTO-overexpressed RA FLS exhibited increased migration, invasion and inflammatory response. We further demonstrated that FTO promoted ADAMTS15 mRNA stability in an m
A-IGF2BP1 dependent manner. Notably, the severity of arthritis was significantly reduced in CIA mice with FB23-2 administration or CIA rats with intra-articular injection of FTO shRNA. Our results illustrate the contribution of FTO-mediated m
A modification to joint damage and inflammation in RA and suggest that FTO might be a potential therapeutic target in RA.</description><subject>Adenosine - analogs & derivatives</subject><subject>Adenosine - metabolism</subject><subject>Alpha-Ketoglutarate-Dependent Dioxygenase FTO - genetics</subject><subject>Alpha-Ketoglutarate-Dependent Dioxygenase FTO - metabolism</subject><subject>Animals</subject><subject>Arthritis, Experimental - genetics</subject><subject>Arthritis, Experimental - metabolism</subject><subject>Arthritis, Experimental - pathology</subject><subject>Arthritis, Rheumatoid - genetics</subject><subject>Arthritis, Rheumatoid - metabolism</subject><subject>Arthritis, Rheumatoid - pathology</subject><subject>Female</subject><subject>Humans</subject><subject>Inflammation - genetics</subject><subject>Inflammation - metabolism</subject><subject>Inflammation - pathology</subject><subject>Male</subject><subject>Methylation</subject><subject>Mice</subject><subject>Rats</subject><subject>RNA Methylation</subject><subject>RNA Stability</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Synovial Membrane - metabolism</subject><subject>Synovial Membrane - pathology</subject><subject>Synoviocytes - metabolism</subject><subject>Synoviocytes - pathology</subject><issn>1879-260X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFjk8LgkAQxZcg0v58hZgvIGxKmseIpFNBeOgmE6464a6yuwZ--zaqc3OYecP7PXgT5m92SRqEMb95bG7Mg7uJEz5jXpTycBslkc8oyy-BFCWhFSVcz3uQEIPbwjZji5Y6BVrUg5PCgBlV9yRsAetaC2PeLqoSSFUtSvnBySUaMbivoxJQ20aTJbNk0wpbI1bfu2Dr7JgfTkE_3F2BotckUY_Fr1v0F3gBh2NFrQ</recordid><startdate>202410</startdate><enddate>202410</enddate><creator>Li, Ruiru</creator><creator>Kuang, Yu</creator><creator>Niu, Yuanyuan</creator><creator>Zhang, Shuoyang</creator><creator>Chen, Simin</creator><creator>Su, Fan</creator><creator>Wang, Jingnan</creator><creator>Lin, Shuibin</creator><creator>Liu, Di</creator><creator>Shen, Chuyu</creator><creator>Liang, Liuqin</creator><creator>Zheng, Song Guo</creator><creator>Jie, Ligang</creator><creator>Xiao, Youjun</creator><creator>Xu, Hanshi</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope></search><sort><creationdate>202410</creationdate><title>FTO-mediated RNA m 6 A methylation regulates synovial aggression and inflammation in rheumatoid arthritis</title><author>Li, Ruiru ; Kuang, Yu ; Niu, Yuanyuan ; Zhang, Shuoyang ; Chen, Simin ; Su, Fan ; Wang, Jingnan ; Lin, Shuibin ; Liu, Di ; Shen, Chuyu ; Liang, Liuqin ; Zheng, Song Guo ; Jie, Ligang ; Xiao, Youjun ; Xu, Hanshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-pubmed_primary_390253733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adenosine - analogs & derivatives</topic><topic>Adenosine - metabolism</topic><topic>Alpha-Ketoglutarate-Dependent Dioxygenase FTO - genetics</topic><topic>Alpha-Ketoglutarate-Dependent Dioxygenase FTO - metabolism</topic><topic>Animals</topic><topic>Arthritis, Experimental - genetics</topic><topic>Arthritis, Experimental - metabolism</topic><topic>Arthritis, Experimental - pathology</topic><topic>Arthritis, Rheumatoid - genetics</topic><topic>Arthritis, Rheumatoid - metabolism</topic><topic>Arthritis, Rheumatoid - pathology</topic><topic>Female</topic><topic>Humans</topic><topic>Inflammation - genetics</topic><topic>Inflammation - metabolism</topic><topic>Inflammation - pathology</topic><topic>Male</topic><topic>Methylation</topic><topic>Mice</topic><topic>Rats</topic><topic>RNA Methylation</topic><topic>RNA Stability</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Synovial Membrane - metabolism</topic><topic>Synovial Membrane - pathology</topic><topic>Synoviocytes - metabolism</topic><topic>Synoviocytes - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Ruiru</creatorcontrib><creatorcontrib>Kuang, Yu</creatorcontrib><creatorcontrib>Niu, Yuanyuan</creatorcontrib><creatorcontrib>Zhang, Shuoyang</creatorcontrib><creatorcontrib>Chen, Simin</creatorcontrib><creatorcontrib>Su, Fan</creatorcontrib><creatorcontrib>Wang, Jingnan</creatorcontrib><creatorcontrib>Lin, Shuibin</creatorcontrib><creatorcontrib>Liu, Di</creatorcontrib><creatorcontrib>Shen, Chuyu</creatorcontrib><creatorcontrib>Liang, Liuqin</creatorcontrib><creatorcontrib>Zheng, Song Guo</creatorcontrib><creatorcontrib>Jie, Ligang</creatorcontrib><creatorcontrib>Xiao, Youjun</creatorcontrib><creatorcontrib>Xu, Hanshi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Biochimica et biophysica acta. Molecular basis of disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Ruiru</au><au>Kuang, Yu</au><au>Niu, Yuanyuan</au><au>Zhang, Shuoyang</au><au>Chen, Simin</au><au>Su, Fan</au><au>Wang, Jingnan</au><au>Lin, Shuibin</au><au>Liu, Di</au><au>Shen, Chuyu</au><au>Liang, Liuqin</au><au>Zheng, Song Guo</au><au>Jie, Ligang</au><au>Xiao, Youjun</au><au>Xu, Hanshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>FTO-mediated RNA m 6 A methylation regulates synovial aggression and inflammation in rheumatoid arthritis</atitle><jtitle>Biochimica et biophysica acta. Molecular basis of disease</jtitle><addtitle>Biochim Biophys Acta Mol Basis Dis</addtitle><date>2024-10</date><risdate>2024</risdate><volume>1870</volume><issue>7</issue><spage>167341</spage><pages>167341-</pages><eissn>1879-260X</eissn><abstract>Fibroblast-like synoviocytes (FLS) plays an important role in synovial inflammation and joint damage in rheumatoid arthritis (RA). As the most abundant mRNA modification, N6-methyladenosine (m
A) is involved in the development of various diseases; however, its role in RA remains to be defined. In this study, we reported the elevated expression of the m
A demethylase fat mass and obesity-associated protein (FTO) in FLS and synovium from RA patients. Functionally, FTO knockdown or treatment with FB23-2, an inhibitor of the mRNA m
A demethylase FTO, inhibited the migration, invasion and inflammatory response of RA FLS, however, FTO-overexpressed RA FLS exhibited increased migration, invasion and inflammatory response. We further demonstrated that FTO promoted ADAMTS15 mRNA stability in an m
A-IGF2BP1 dependent manner. Notably, the severity of arthritis was significantly reduced in CIA mice with FB23-2 administration or CIA rats with intra-articular injection of FTO shRNA. Our results illustrate the contribution of FTO-mediated m
A modification to joint damage and inflammation in RA and suggest that FTO might be a potential therapeutic target in RA.</abstract><cop>Netherlands</cop><pmid>39025373</pmid></addata></record> |
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| subjects | Adenosine - analogs & derivatives Adenosine - metabolism Alpha-Ketoglutarate-Dependent Dioxygenase FTO - genetics Alpha-Ketoglutarate-Dependent Dioxygenase FTO - metabolism Animals Arthritis, Experimental - genetics Arthritis, Experimental - metabolism Arthritis, Experimental - pathology Arthritis, Rheumatoid - genetics Arthritis, Rheumatoid - metabolism Arthritis, Rheumatoid - pathology Female Humans Inflammation - genetics Inflammation - metabolism Inflammation - pathology Male Methylation Mice Rats RNA Methylation RNA Stability RNA, Messenger - genetics RNA, Messenger - metabolism Synovial Membrane - metabolism Synovial Membrane - pathology Synoviocytes - metabolism Synoviocytes - pathology |
| title | FTO-mediated RNA m 6 A methylation regulates synovial aggression and inflammation in rheumatoid arthritis |
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