A Novel Regulator of Macrophage Activation: miR-223 in Obesity-Associated Adipose Tissue Inflammation
Macrophage activation plays a crucial role in regulating adipose tissue inflammation and is a major contributor to the pathogenesis of obesity-associated cardiovascular diseases. On various types of stimuli, macrophages respond with either classic (M1) or alternative (M2) activation. M1- and M2-medi...
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| Veröffentlicht in: | Circulation (New York, N.Y.) N.Y.), 2012-06, Vol.125 (23), p.2892-2903 |
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| creator | GUOQING ZHUANG CONG MENG CHAODONG WU BEIYAN ZHOU XIN GUO CHERUKU, Patali S LEI SHI HANG XU HONGGUI LI GANG WANG EVANS, Ashley R SAFE, Stephen |
| description | Macrophage activation plays a crucial role in regulating adipose tissue inflammation and is a major contributor to the pathogenesis of obesity-associated cardiovascular diseases. On various types of stimuli, macrophages respond with either classic (M1) or alternative (M2) activation. M1- and M2-mediated signaling pathways and corresponding cytokine production profiles are not completely understood. The discovery of microRNAs provides a new opportunity to understand this complicated but crucial network for macrophage activation and adipose tissue function.
We have examined the activity of microRNA-223 (miR-223) and its role in controlling macrophage functions in adipose tissue inflammation and systemic insulin resistance. miR-223(-/-) mice on a high-fat diet exhibited an increased severity of systemic insulin resistance compared with wild-type mice that was accompanied by a marked increase in adipose tissue inflammation. The specific regulatory effects of miR-223 in myeloid cell-mediated regulation of adipose tissue inflammation and insulin resistance were then confirmed by transplantation analysis. Moreover, using bone marrow-derived macrophages, we demonstrated that miR-223 is a novel regulator of macrophage polarization, which suppresses classic proinflammatory pathways and enhances the alternative antiinflammatory responses. In addition, we identified Pknox1 as a genuine miR-223 target gene and an essential regulator for macrophage polarization.
For the first time, this study demonstrates that miR-223 acts to inhibit Pknox1, suppressing proinflammatory activation of macrophages; thus, it is a crucial regulator of macrophage polarization and protects against diet-induced adipose tissue inflammatory response and systemic insulin resistance. |
| doi_str_mv | 10.1161/CIRCULATIONAHA.111.087817 |
| format | Article |
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We have examined the activity of microRNA-223 (miR-223) and its role in controlling macrophage functions in adipose tissue inflammation and systemic insulin resistance. miR-223(-/-) mice on a high-fat diet exhibited an increased severity of systemic insulin resistance compared with wild-type mice that was accompanied by a marked increase in adipose tissue inflammation. The specific regulatory effects of miR-223 in myeloid cell-mediated regulation of adipose tissue inflammation and insulin resistance were then confirmed by transplantation analysis. Moreover, using bone marrow-derived macrophages, we demonstrated that miR-223 is a novel regulator of macrophage polarization, which suppresses classic proinflammatory pathways and enhances the alternative antiinflammatory responses. In addition, we identified Pknox1 as a genuine miR-223 target gene and an essential regulator for macrophage polarization.
For the first time, this study demonstrates that miR-223 acts to inhibit Pknox1, suppressing proinflammatory activation of macrophages; thus, it is a crucial regulator of macrophage polarization and protects against diet-induced adipose tissue inflammatory response and systemic insulin resistance.</description><identifier>ISSN: 0009-7322</identifier><identifier>EISSN: 1524-4539</identifier><identifier>DOI: 10.1161/CIRCULATIONAHA.111.087817</identifier><identifier>PMID: 22580331</identifier><identifier>CODEN: CIRCAZ</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott Williams & Wilkins</publisher><subject>Adipocytes - cytology ; Adipocytes - immunology ; Adipose Tissue - cytology ; Adipose Tissue - immunology ; Animals ; Biological and medical sciences ; Blood and lymphatic vessels ; Bone Marrow Transplantation ; Cardiology. Vascular system ; Cell Differentiation - genetics ; Cell Differentiation - immunology ; Cell Polarity - genetics ; Cell Polarity - immunology ; Cells, Cultured ; Coculture Techniques ; Coronary heart disease ; Dietary Fats - pharmacology ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Heart ; Homeodomain Proteins - genetics ; Homeodomain Proteins - immunology ; Homeodomain Proteins - metabolism ; Immunophenotyping ; Inflammation - immunology ; Insulin Resistance - immunology ; Macrophages - cytology ; Macrophages - immunology ; Male ; Medical sciences ; Mice ; Mice, Inbred C57BL ; MicroRNAs - immunology ; MicroRNAs - metabolism ; Myeloid Cells - cytology ; Myeloid Cells - immunology ; Obesity - immunology ; Predictive Value of Tests ; RNA, Small Interfering - genetics</subject><ispartof>Circulation (New York, N.Y.), 2012-06, Vol.125 (23), p.2892-2903</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c347t-6c5b51f6b09890bed504079cba3bb41e1d10d621fdd0c7b8f0641266bc9c59253</citedby><cites>FETCH-LOGICAL-c347t-6c5b51f6b09890bed504079cba3bb41e1d10d621fdd0c7b8f0641266bc9c59253</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,3674,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25991010$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22580331$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>GUOQING ZHUANG</creatorcontrib><creatorcontrib>CONG MENG</creatorcontrib><creatorcontrib>CHAODONG WU</creatorcontrib><creatorcontrib>BEIYAN ZHOU</creatorcontrib><creatorcontrib>XIN GUO</creatorcontrib><creatorcontrib>CHERUKU, Patali S</creatorcontrib><creatorcontrib>LEI SHI</creatorcontrib><creatorcontrib>HANG XU</creatorcontrib><creatorcontrib>HONGGUI LI</creatorcontrib><creatorcontrib>GANG WANG</creatorcontrib><creatorcontrib>EVANS, Ashley R</creatorcontrib><creatorcontrib>SAFE, Stephen</creatorcontrib><title>A Novel Regulator of Macrophage Activation: miR-223 in Obesity-Associated Adipose Tissue Inflammation</title><title>Circulation (New York, N.Y.)</title><addtitle>Circulation</addtitle><description>Macrophage activation plays a crucial role in regulating adipose tissue inflammation and is a major contributor to the pathogenesis of obesity-associated cardiovascular diseases. On various types of stimuli, macrophages respond with either classic (M1) or alternative (M2) activation. M1- and M2-mediated signaling pathways and corresponding cytokine production profiles are not completely understood. The discovery of microRNAs provides a new opportunity to understand this complicated but crucial network for macrophage activation and adipose tissue function.
We have examined the activity of microRNA-223 (miR-223) and its role in controlling macrophage functions in adipose tissue inflammation and systemic insulin resistance. miR-223(-/-) mice on a high-fat diet exhibited an increased severity of systemic insulin resistance compared with wild-type mice that was accompanied by a marked increase in adipose tissue inflammation. The specific regulatory effects of miR-223 in myeloid cell-mediated regulation of adipose tissue inflammation and insulin resistance were then confirmed by transplantation analysis. Moreover, using bone marrow-derived macrophages, we demonstrated that miR-223 is a novel regulator of macrophage polarization, which suppresses classic proinflammatory pathways and enhances the alternative antiinflammatory responses. In addition, we identified Pknox1 as a genuine miR-223 target gene and an essential regulator for macrophage polarization.
For the first time, this study demonstrates that miR-223 acts to inhibit Pknox1, suppressing proinflammatory activation of macrophages; thus, it is a crucial regulator of macrophage polarization and protects against diet-induced adipose tissue inflammatory response and systemic insulin resistance.</description><subject>Adipocytes - cytology</subject><subject>Adipocytes - immunology</subject><subject>Adipose Tissue - cytology</subject><subject>Adipose Tissue - immunology</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Blood and lymphatic vessels</subject><subject>Bone Marrow Transplantation</subject><subject>Cardiology. Vascular system</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Differentiation - immunology</subject><subject>Cell Polarity - genetics</subject><subject>Cell Polarity - immunology</subject><subject>Cells, Cultured</subject><subject>Coculture Techniques</subject><subject>Coronary heart disease</subject><subject>Dietary Fats - pharmacology</subject><subject>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</subject><subject>Heart</subject><subject>Homeodomain Proteins - genetics</subject><subject>Homeodomain Proteins - immunology</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Immunophenotyping</subject><subject>Inflammation - immunology</subject><subject>Insulin Resistance - immunology</subject><subject>Macrophages - cytology</subject><subject>Macrophages - immunology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>MicroRNAs - immunology</subject><subject>MicroRNAs - metabolism</subject><subject>Myeloid Cells - cytology</subject><subject>Myeloid Cells - immunology</subject><subject>Obesity - immunology</subject><subject>Predictive Value of Tests</subject><subject>RNA, Small Interfering - genetics</subject><issn>0009-7322</issn><issn>1524-4539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkE1LxDAQhoMoun78BYkHwUt1JmnaxltZ_FhYXVjWc0nSVCNtszat4L-3uqviaZjheWeYh5AzhEvEBK-ms-X0aZ6vZovH_D4fZ3gJWZphukMmKFgcxYLLXTIBABmlnLEDchjC69gmPBX75IAxkQHnOCE2p4_-3dZ0aZ-HWvW-o76iD8p0fv2ini3NTe_eVe98e00bt4wY49S1dKFtcP1HlIfgjVO9LWleurUPlq5cCIOls7aqVdN8R4_JXqXqYE-29Yg83d6spvfRfHE3m-bzyPA47aPECC2wSjTITIK2pYAYUmm04lrHaLFEKBOGVVmCSXVWQRIjSxJtpBGSCX5ELjZ7151_G2zoi8YFY-tatdYPoUBggBKFiEdUbtDx0xA6WxXrzjWq-xih4sty8d_yOMNiY3nMnm7PDLqx5W_yR-sInG8BFYyqq061xoU_TkiJgMA_AZGchkU</recordid><startdate>20120612</startdate><enddate>20120612</enddate><creator>GUOQING ZHUANG</creator><creator>CONG MENG</creator><creator>CHAODONG WU</creator><creator>BEIYAN ZHOU</creator><creator>XIN GUO</creator><creator>CHERUKU, Patali S</creator><creator>LEI SHI</creator><creator>HANG XU</creator><creator>HONGGUI LI</creator><creator>GANG WANG</creator><creator>EVANS, Ashley R</creator><creator>SAFE, Stephen</creator><general>Lippincott Williams & Wilkins</general><scope>IQODW</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>20120612</creationdate><title>A Novel Regulator of Macrophage Activation: miR-223 in Obesity-Associated Adipose Tissue Inflammation</title><author>GUOQING ZHUANG ; CONG MENG ; CHAODONG WU ; BEIYAN ZHOU ; XIN GUO ; CHERUKU, Patali S ; LEI SHI ; HANG XU ; HONGGUI LI ; GANG WANG ; EVANS, Ashley R ; SAFE, Stephen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c347t-6c5b51f6b09890bed504079cba3bb41e1d10d621fdd0c7b8f0641266bc9c59253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adipocytes - cytology</topic><topic>Adipocytes - immunology</topic><topic>Adipose Tissue - cytology</topic><topic>Adipose Tissue - immunology</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Blood and lymphatic vessels</topic><topic>Bone Marrow Transplantation</topic><topic>Cardiology. Vascular system</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Differentiation - immunology</topic><topic>Cell Polarity - genetics</topic><topic>Cell Polarity - immunology</topic><topic>Cells, Cultured</topic><topic>Coculture Techniques</topic><topic>Coronary heart disease</topic><topic>Dietary Fats - pharmacology</topic><topic>Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous</topic><topic>Heart</topic><topic>Homeodomain Proteins - genetics</topic><topic>Homeodomain Proteins - immunology</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Immunophenotyping</topic><topic>Inflammation - immunology</topic><topic>Insulin Resistance - immunology</topic><topic>Macrophages - cytology</topic><topic>Macrophages - immunology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>MicroRNAs - immunology</topic><topic>MicroRNAs - metabolism</topic><topic>Myeloid Cells - cytology</topic><topic>Myeloid Cells - immunology</topic><topic>Obesity - immunology</topic><topic>Predictive Value of Tests</topic><topic>RNA, Small Interfering - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>GUOQING ZHUANG</creatorcontrib><creatorcontrib>CONG MENG</creatorcontrib><creatorcontrib>CHAODONG WU</creatorcontrib><creatorcontrib>BEIYAN ZHOU</creatorcontrib><creatorcontrib>XIN GUO</creatorcontrib><creatorcontrib>CHERUKU, Patali S</creatorcontrib><creatorcontrib>LEI SHI</creatorcontrib><creatorcontrib>HANG XU</creatorcontrib><creatorcontrib>HONGGUI LI</creatorcontrib><creatorcontrib>GANG WANG</creatorcontrib><creatorcontrib>EVANS, Ashley R</creatorcontrib><creatorcontrib>SAFE, Stephen</creatorcontrib><collection>Pascal-Francis</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>Circulation (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>GUOQING ZHUANG</au><au>CONG MENG</au><au>CHAODONG WU</au><au>BEIYAN ZHOU</au><au>XIN GUO</au><au>CHERUKU, Patali S</au><au>LEI SHI</au><au>HANG XU</au><au>HONGGUI LI</au><au>GANG WANG</au><au>EVANS, Ashley R</au><au>SAFE, Stephen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Novel Regulator of Macrophage Activation: miR-223 in Obesity-Associated Adipose Tissue Inflammation</atitle><jtitle>Circulation (New York, N.Y.)</jtitle><addtitle>Circulation</addtitle><date>2012-06-12</date><risdate>2012</risdate><volume>125</volume><issue>23</issue><spage>2892</spage><epage>2903</epage><pages>2892-2903</pages><issn>0009-7322</issn><eissn>1524-4539</eissn><coden>CIRCAZ</coden><abstract>Macrophage activation plays a crucial role in regulating adipose tissue inflammation and is a major contributor to the pathogenesis of obesity-associated cardiovascular diseases. On various types of stimuli, macrophages respond with either classic (M1) or alternative (M2) activation. M1- and M2-mediated signaling pathways and corresponding cytokine production profiles are not completely understood. The discovery of microRNAs provides a new opportunity to understand this complicated but crucial network for macrophage activation and adipose tissue function.
We have examined the activity of microRNA-223 (miR-223) and its role in controlling macrophage functions in adipose tissue inflammation and systemic insulin resistance. miR-223(-/-) mice on a high-fat diet exhibited an increased severity of systemic insulin resistance compared with wild-type mice that was accompanied by a marked increase in adipose tissue inflammation. The specific regulatory effects of miR-223 in myeloid cell-mediated regulation of adipose tissue inflammation and insulin resistance were then confirmed by transplantation analysis. Moreover, using bone marrow-derived macrophages, we demonstrated that miR-223 is a novel regulator of macrophage polarization, which suppresses classic proinflammatory pathways and enhances the alternative antiinflammatory responses. In addition, we identified Pknox1 as a genuine miR-223 target gene and an essential regulator for macrophage polarization.
For the first time, this study demonstrates that miR-223 acts to inhibit Pknox1, suppressing proinflammatory activation of macrophages; thus, it is a crucial regulator of macrophage polarization and protects against diet-induced adipose tissue inflammatory response and systemic insulin resistance.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott Williams & Wilkins</pub><pmid>22580331</pmid><doi>10.1161/CIRCULATIONAHA.111.087817</doi><tpages>12</tpages></addata></record> |
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| ispartof | Circulation (New York, N.Y.), 2012-06, Vol.125 (23), p.2892-2903 |
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| subjects | Adipocytes - cytology Adipocytes - immunology Adipose Tissue - cytology Adipose Tissue - immunology Animals Biological and medical sciences Blood and lymphatic vessels Bone Marrow Transplantation Cardiology. Vascular system Cell Differentiation - genetics Cell Differentiation - immunology Cell Polarity - genetics Cell Polarity - immunology Cells, Cultured Coculture Techniques Coronary heart disease Dietary Fats - pharmacology Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous Heart Homeodomain Proteins - genetics Homeodomain Proteins - immunology Homeodomain Proteins - metabolism Immunophenotyping Inflammation - immunology Insulin Resistance - immunology Macrophages - cytology Macrophages - immunology Male Medical sciences Mice Mice, Inbred C57BL MicroRNAs - immunology MicroRNAs - metabolism Myeloid Cells - cytology Myeloid Cells - immunology Obesity - immunology Predictive Value of Tests RNA, Small Interfering - genetics |
| title | A Novel Regulator of Macrophage Activation: miR-223 in Obesity-Associated Adipose Tissue Inflammation |
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