Eplerenone inhibits atrial fibrosis in mutant TGF-β1 transgenic mice
The purpose of the present study was to study the impacts of eplerenone （EPL）, an antagonist of mineralocorticoid receptors （MR）, on atrial fibrosis in a mouse model with selective fibrosis in the atrium, and to explore the possible mechanisms. Using mutant TGF-β1 transgenic （Tx） mice, we first demo...
Gespeichert in:
| Veröffentlicht in: | Science China. Life sciences 2016-10, Vol.59 (10), p.1042-1047 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1047 |
|---|---|
| container_issue | 10 |
| container_start_page | 1042 |
| container_title | Science China. Life sciences |
| container_volume | 59 |
| creator | Chen, Xiaoqing Zhang, Wuchang Wang, Qian Du, Lili Yi, Yi Liu, Yan Liu, Xu Duan, Shengzhong |
| description | The purpose of the present study was to study the impacts of eplerenone （EPL）, an antagonist of mineralocorticoid receptors （MR）, on atrial fibrosis in a mouse model with selective fibrosis in the atrium, and to explore the possible mechanisms. Using mutant TGF-β1 transgenic （Tx） mice, we first demonstrated that EPL inhibited atrial fibrosis specifically and decreased mac- rophage accumulation in the atria of these mice. Results from immunohistochemistry and western blotting showed that EPL attenuated protein expression of fibrosis-related molecules such as connective tissue growth factor （CTGF） and fibronectin in the atria of Tx mice. In culture, EPL inhibited gene expression of fibrosis-related molecules such as fibronectin, ct-SMA, and CTGF in TGF-β1-stimulated atrial fibroblasts, Finally, using a co-culture system, we showed that TGF-β1 stimulated atrial fi- broblasts induced migration of macrophages and this was blocked by EPL. EPL also blocked TGF-β1 induced gene expression of intedeukin-6 （IL-6） in atrial fibroblasts. Therefore, we conclude that EPL attenuated atrial fibrosis and macrophage infiltra- tion in Tx mice. TGF-I31 and IL-6 were involved in the impacts of EPL on activation of atrial fibroblasts and interactions be- tween fibroblasts and macrophages. |
| doi_str_mv | 10.1007/s11427-016-0037-y |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1826706821</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><cqvip_id>670234575</cqvip_id><sourcerecordid>1826706821</sourcerecordid><originalsourceid>FETCH-LOGICAL-c329y-21c9bc1d1cdee03ee3efce47eb2c8cd5f2d7d35a42006d36b0bff7e39c7b781e3</originalsourceid><addsrcrecordid>eNp9kE1OwzAQhS0EohX0AGxQxIqNwT9J7CxR1RakSmzK2kqcSesqcVo7WeRaHIQz4SqlS2YzI817TzMfQg-UvFBCxKunNGYCE5piQrjAwxWaUplmmEqZXYc5FTEWnCQTNPN-T0JxTpgQt2jCBOdcyGyKFotDDQ5sayEydmcK0_ko75zJ66gyhWu98WERNX2X2y7arJb455tGncut34I1OmqMhnt0U-W1h9m536Gv5WIzf8frz9XH_G2NNWfZgBnVWaFpSXUJQDgAh0pDLKBgWuoyqVgpSp7kMSMkLXlakKKqBPBMi0JICvwOPY-5B9cee_CdaozXUNe5hbb3ikqWCpJKRoOUjlIdfvAOKnVwpsndoChRJ4BqBKgCQHUCqIbgeTzH90UD5cXxhysI2CjwYWW34NS-7Z0NL_-b-nS-ZNfa7TH4LsHhWMbjRCT8F6W5iFg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1826706821</pqid></control><display><type>article</type><title>Eplerenone inhibits atrial fibrosis in mutant TGF-β1 transgenic mice</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><source>SpringerLink Journals - AutoHoldings</source><creator>Chen, Xiaoqing ; Zhang, Wuchang ; Wang, Qian ; Du, Lili ; Yi, Yi ; Liu, Yan ; Liu, Xu ; Duan, Shengzhong</creator><creatorcontrib>Chen, Xiaoqing ; Zhang, Wuchang ; Wang, Qian ; Du, Lili ; Yi, Yi ; Liu, Yan ; Liu, Xu ; Duan, Shengzhong</creatorcontrib><description>The purpose of the present study was to study the impacts of eplerenone （EPL）, an antagonist of mineralocorticoid receptors （MR）, on atrial fibrosis in a mouse model with selective fibrosis in the atrium, and to explore the possible mechanisms. Using mutant TGF-β1 transgenic （Tx） mice, we first demonstrated that EPL inhibited atrial fibrosis specifically and decreased mac- rophage accumulation in the atria of these mice. Results from immunohistochemistry and western blotting showed that EPL attenuated protein expression of fibrosis-related molecules such as connective tissue growth factor （CTGF） and fibronectin in the atria of Tx mice. In culture, EPL inhibited gene expression of fibrosis-related molecules such as fibronectin, ct-SMA, and CTGF in TGF-β1-stimulated atrial fibroblasts, Finally, using a co-culture system, we showed that TGF-β1 stimulated atrial fi- broblasts induced migration of macrophages and this was blocked by EPL. EPL also blocked TGF-β1 induced gene expression of intedeukin-6 （IL-6） in atrial fibroblasts. Therefore, we conclude that EPL attenuated atrial fibrosis and macrophage infiltra- tion in Tx mice. TGF-I31 and IL-6 were involved in the impacts of EPL on activation of atrial fibroblasts and interactions be- tween fibroblasts and macrophages.</description><identifier>ISSN: 1674-7305</identifier><identifier>EISSN: 1869-1889</identifier><identifier>DOI: 10.1007/s11427-016-0037-y</identifier><identifier>PMID: 27333789</identifier><language>eng</language><publisher>Beijing: Science China Press</publisher><subject>Animals ; Biomedical and Life Sciences ; Blotting, Western ; Cells, Cultured ; Coculture Techniques ; Connective Tissue Growth Factor - genetics ; Connective Tissue Growth Factor - metabolism ; Fibroblasts - cytology ; Fibroblasts - drug effects ; Fibroblasts - metabolism ; Fibronectins - genetics ; Fibronectins - metabolism ; Fibrosis - genetics ; Fibrosis - prevention & control ; Gene Expression - drug effects ; Heart Atria - metabolism ; Heart Atria - pathology ; Interleukin-6 - genetics ; Interleukin-6 - metabolism ; Life Sciences ; Macrophages - cytology ; Macrophages - drug effects ; Macrophages - metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microscopy, Fluorescence ; Mineralocorticoid Receptor Antagonists - pharmacology ; Mutation ; Myocardium - metabolism ; Myocardium - pathology ; Research Paper ; Reverse Transcriptase Polymerase Chain Reaction ; Spironolactone - analogs & derivatives ; Spironolactone - pharmacology ; TGF-β1 ; Transforming Growth Factor beta1 - genetics ; Transforming Growth Factor beta1 - metabolism ; Transforming Growth Factor beta1 - pharmacology ; Western印迹 ; 基因突变 ; 心房 ; 成纤维细胞 ; 纤维化 ; 结缔组织生长因子 ; 转基因小鼠</subject><ispartof>Science China. Life sciences, 2016-10, Vol.59 (10), p.1042-1047</ispartof><rights>The Author(s) 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c329y-21c9bc1d1cdee03ee3efce47eb2c8cd5f2d7d35a42006d36b0bff7e39c7b781e3</citedby><cites>FETCH-LOGICAL-c329y-21c9bc1d1cdee03ee3efce47eb2c8cd5f2d7d35a42006d36b0bff7e39c7b781e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://image.cqvip.com/vip1000/qk/60112X/60112X.jpg</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11427-016-0037-y$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11427-016-0037-y$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27333789$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Xiaoqing</creatorcontrib><creatorcontrib>Zhang, Wuchang</creatorcontrib><creatorcontrib>Wang, Qian</creatorcontrib><creatorcontrib>Du, Lili</creatorcontrib><creatorcontrib>Yi, Yi</creatorcontrib><creatorcontrib>Liu, Yan</creatorcontrib><creatorcontrib>Liu, Xu</creatorcontrib><creatorcontrib>Duan, Shengzhong</creatorcontrib><title>Eplerenone inhibits atrial fibrosis in mutant TGF-β1 transgenic mice</title><title>Science China. Life sciences</title><addtitle>Sci. China Life Sci</addtitle><addtitle>Sci China Life Sci</addtitle><description>The purpose of the present study was to study the impacts of eplerenone （EPL）, an antagonist of mineralocorticoid receptors （MR）, on atrial fibrosis in a mouse model with selective fibrosis in the atrium, and to explore the possible mechanisms. Using mutant TGF-β1 transgenic （Tx） mice, we first demonstrated that EPL inhibited atrial fibrosis specifically and decreased mac- rophage accumulation in the atria of these mice. Results from immunohistochemistry and western blotting showed that EPL attenuated protein expression of fibrosis-related molecules such as connective tissue growth factor （CTGF） and fibronectin in the atria of Tx mice. In culture, EPL inhibited gene expression of fibrosis-related molecules such as fibronectin, ct-SMA, and CTGF in TGF-β1-stimulated atrial fibroblasts, Finally, using a co-culture system, we showed that TGF-β1 stimulated atrial fi- broblasts induced migration of macrophages and this was blocked by EPL. EPL also blocked TGF-β1 induced gene expression of intedeukin-6 （IL-6） in atrial fibroblasts. Therefore, we conclude that EPL attenuated atrial fibrosis and macrophage infiltra- tion in Tx mice. TGF-I31 and IL-6 were involved in the impacts of EPL on activation of atrial fibroblasts and interactions be- tween fibroblasts and macrophages.</description><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Blotting, Western</subject><subject>Cells, Cultured</subject><subject>Coculture Techniques</subject><subject>Connective Tissue Growth Factor - genetics</subject><subject>Connective Tissue Growth Factor - metabolism</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - drug effects</subject><subject>Fibroblasts - metabolism</subject><subject>Fibronectins - genetics</subject><subject>Fibronectins - metabolism</subject><subject>Fibrosis - genetics</subject><subject>Fibrosis - prevention & control</subject><subject>Gene Expression - drug effects</subject><subject>Heart Atria - metabolism</subject><subject>Heart Atria - pathology</subject><subject>Interleukin-6 - genetics</subject><subject>Interleukin-6 - metabolism</subject><subject>Life Sciences</subject><subject>Macrophages - cytology</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Microscopy, Fluorescence</subject><subject>Mineralocorticoid Receptor Antagonists - pharmacology</subject><subject>Mutation</subject><subject>Myocardium - metabolism</subject><subject>Myocardium - pathology</subject><subject>Research Paper</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Spironolactone - analogs & derivatives</subject><subject>Spironolactone - pharmacology</subject><subject>TGF-β1</subject><subject>Transforming Growth Factor beta1 - genetics</subject><subject>Transforming Growth Factor beta1 - metabolism</subject><subject>Transforming Growth Factor beta1 - pharmacology</subject><subject>Western印迹</subject><subject>基因突变</subject><subject>心房</subject><subject>成纤维细胞</subject><subject>纤维化</subject><subject>结缔组织生长因子</subject><subject>转基因小鼠</subject><issn>1674-7305</issn><issn>1869-1889</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNp9kE1OwzAQhS0EohX0AGxQxIqNwT9J7CxR1RakSmzK2kqcSesqcVo7WeRaHIQz4SqlS2YzI817TzMfQg-UvFBCxKunNGYCE5piQrjAwxWaUplmmEqZXYc5FTEWnCQTNPN-T0JxTpgQt2jCBOdcyGyKFotDDQ5sayEydmcK0_ko75zJ66gyhWu98WERNX2X2y7arJb455tGncut34I1OmqMhnt0U-W1h9m536Gv5WIzf8frz9XH_G2NNWfZgBnVWaFpSXUJQDgAh0pDLKBgWuoyqVgpSp7kMSMkLXlakKKqBPBMi0JICvwOPY-5B9cee_CdaozXUNe5hbb3ikqWCpJKRoOUjlIdfvAOKnVwpsndoChRJ4BqBKgCQHUCqIbgeTzH90UD5cXxhysI2CjwYWW34NS-7Z0NL_-b-nS-ZNfa7TH4LsHhWMbjRCT8F6W5iFg</recordid><startdate>20161001</startdate><enddate>20161001</enddate><creator>Chen, Xiaoqing</creator><creator>Zhang, Wuchang</creator><creator>Wang, Qian</creator><creator>Du, Lili</creator><creator>Yi, Yi</creator><creator>Liu, Yan</creator><creator>Liu, Xu</creator><creator>Duan, Shengzhong</creator><general>Science China Press</general><scope>2RA</scope><scope>92L</scope><scope>CQIGP</scope><scope>~WA</scope><scope>C6C</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>20161001</creationdate><title>Eplerenone inhibits atrial fibrosis in mutant TGF-β1 transgenic mice</title><author>Chen, Xiaoqing ; Zhang, Wuchang ; Wang, Qian ; Du, Lili ; Yi, Yi ; Liu, Yan ; Liu, Xu ; Duan, Shengzhong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c329y-21c9bc1d1cdee03ee3efce47eb2c8cd5f2d7d35a42006d36b0bff7e39c7b781e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Blotting, Western</topic><topic>Cells, Cultured</topic><topic>Coculture Techniques</topic><topic>Connective Tissue Growth Factor - genetics</topic><topic>Connective Tissue Growth Factor - metabolism</topic><topic>Fibroblasts - cytology</topic><topic>Fibroblasts - drug effects</topic><topic>Fibroblasts - metabolism</topic><topic>Fibronectins - genetics</topic><topic>Fibronectins - metabolism</topic><topic>Fibrosis - genetics</topic><topic>Fibrosis - prevention & control</topic><topic>Gene Expression - drug effects</topic><topic>Heart Atria - metabolism</topic><topic>Heart Atria - pathology</topic><topic>Interleukin-6 - genetics</topic><topic>Interleukin-6 - metabolism</topic><topic>Life Sciences</topic><topic>Macrophages - cytology</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Microscopy, Fluorescence</topic><topic>Mineralocorticoid Receptor Antagonists - pharmacology</topic><topic>Mutation</topic><topic>Myocardium - metabolism</topic><topic>Myocardium - pathology</topic><topic>Research Paper</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Spironolactone - analogs & derivatives</topic><topic>Spironolactone - pharmacology</topic><topic>TGF-β1</topic><topic>Transforming Growth Factor beta1 - genetics</topic><topic>Transforming Growth Factor beta1 - metabolism</topic><topic>Transforming Growth Factor beta1 - pharmacology</topic><topic>Western印迹</topic><topic>基因突变</topic><topic>心房</topic><topic>成纤维细胞</topic><topic>纤维化</topic><topic>结缔组织生长因子</topic><topic>转基因小鼠</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Xiaoqing</creatorcontrib><creatorcontrib>Zhang, Wuchang</creatorcontrib><creatorcontrib>Wang, Qian</creatorcontrib><creatorcontrib>Du, Lili</creatorcontrib><creatorcontrib>Yi, Yi</creatorcontrib><creatorcontrib>Liu, Yan</creatorcontrib><creatorcontrib>Liu, Xu</creatorcontrib><creatorcontrib>Duan, Shengzhong</creatorcontrib><collection>中文科技期刊数据库</collection><collection>中文科技期刊数据库-CALIS站点</collection><collection>中文科技期刊数据库-7.0平台</collection><collection>中文科技期刊数据库- 镜像站点</collection><collection>Springer Nature OA Free Journals</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>Science China. Life sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Xiaoqing</au><au>Zhang, Wuchang</au><au>Wang, Qian</au><au>Du, Lili</au><au>Yi, Yi</au><au>Liu, Yan</au><au>Liu, Xu</au><au>Duan, Shengzhong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Eplerenone inhibits atrial fibrosis in mutant TGF-β1 transgenic mice</atitle><jtitle>Science China. Life sciences</jtitle><stitle>Sci. China Life Sci</stitle><addtitle>Sci China Life Sci</addtitle><date>2016-10-01</date><risdate>2016</risdate><volume>59</volume><issue>10</issue><spage>1042</spage><epage>1047</epage><pages>1042-1047</pages><issn>1674-7305</issn><eissn>1869-1889</eissn><abstract>The purpose of the present study was to study the impacts of eplerenone （EPL）, an antagonist of mineralocorticoid receptors （MR）, on atrial fibrosis in a mouse model with selective fibrosis in the atrium, and to explore the possible mechanisms. Using mutant TGF-β1 transgenic （Tx） mice, we first demonstrated that EPL inhibited atrial fibrosis specifically and decreased mac- rophage accumulation in the atria of these mice. Results from immunohistochemistry and western blotting showed that EPL attenuated protein expression of fibrosis-related molecules such as connective tissue growth factor （CTGF） and fibronectin in the atria of Tx mice. In culture, EPL inhibited gene expression of fibrosis-related molecules such as fibronectin, ct-SMA, and CTGF in TGF-β1-stimulated atrial fibroblasts, Finally, using a co-culture system, we showed that TGF-β1 stimulated atrial fi- broblasts induced migration of macrophages and this was blocked by EPL. EPL also blocked TGF-β1 induced gene expression of intedeukin-6 （IL-6） in atrial fibroblasts. Therefore, we conclude that EPL attenuated atrial fibrosis and macrophage infiltra- tion in Tx mice. TGF-I31 and IL-6 were involved in the impacts of EPL on activation of atrial fibroblasts and interactions be- tween fibroblasts and macrophages.</abstract><cop>Beijing</cop><pub>Science China Press</pub><pmid>27333789</pmid><doi>10.1007/s11427-016-0037-y</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1674-7305 |
| ispartof | Science China. Life sciences, 2016-10, Vol.59 (10), p.1042-1047 |
| issn | 1674-7305 1869-1889 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1826706821 |
| source | MEDLINE; Alma/SFX Local Collection; SpringerLink Journals - AutoHoldings |
| subjects | Animals Biomedical and Life Sciences Blotting, Western Cells, Cultured Coculture Techniques Connective Tissue Growth Factor - genetics Connective Tissue Growth Factor - metabolism Fibroblasts - cytology Fibroblasts - drug effects Fibroblasts - metabolism Fibronectins - genetics Fibronectins - metabolism Fibrosis - genetics Fibrosis - prevention & control Gene Expression - drug effects Heart Atria - metabolism Heart Atria - pathology Interleukin-6 - genetics Interleukin-6 - metabolism Life Sciences Macrophages - cytology Macrophages - drug effects Macrophages - metabolism Male Mice Mice, Inbred C57BL Mice, Transgenic Microscopy, Fluorescence Mineralocorticoid Receptor Antagonists - pharmacology Mutation Myocardium - metabolism Myocardium - pathology Research Paper Reverse Transcriptase Polymerase Chain Reaction Spironolactone - analogs & derivatives Spironolactone - pharmacology TGF-β1 Transforming Growth Factor beta1 - genetics Transforming Growth Factor beta1 - metabolism Transforming Growth Factor beta1 - pharmacology Western印迹 基因突变 心房 成纤维细胞 纤维化 结缔组织生长因子 转基因小鼠 |
| title | Eplerenone inhibits atrial fibrosis in mutant TGF-β1 transgenic mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T14%3A52%3A54IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Eplerenone%20inhibits%20atrial%20fibrosis%20in%20mutant%20TGF-%CE%B21%20transgenic%20mice&rft.jtitle=Science%20China.%20Life%20sciences&rft.au=Chen,%20Xiaoqing&rft.date=2016-10-01&rft.volume=59&rft.issue=10&rft.spage=1042&rft.epage=1047&rft.pages=1042-1047&rft.issn=1674-7305&rft.eissn=1869-1889&rft_id=info:doi/10.1007/s11427-016-0037-y&rft_dat=%3Cproquest_cross%3E1826706821%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1826706821&rft_id=info:pmid/27333789&rft_cqvip_id=670234575&rfr_iscdi=true |