Deoxycholic Acid Is Involved in the Proliferation and Migration of Vascular Smooth Muscle Cells
Obesity is increasingly becoming associated with increased risk of atherosclerosis. Serum levels of the bile acid deoxycholic acid (DCA) are elevated in mice with obesity induced by a high-fat (HF) diet. Therefore, we investigated the influence of DCA on the functions of vascular smooth muscle cells...
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| Veröffentlicht in: | Journal of Nutritional Science and Vitaminology 2014, Vol.60(6), pp.450-454 |
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| creator | SHIMIZU, Hidehisa HAGIO, Masahito IWAYA, Hitoshi TSUNEKI, Ikuya LEE, Ja-Young FUKIYA, Satoru YOKOTA, Atsushi MIYAZAKI, Hitoshi HARA, Hiroshi ISHIZUKA, Satoshi |
| description | Obesity is increasingly becoming associated with increased risk of atherosclerosis. Serum levels of the bile acid deoxycholic acid (DCA) are elevated in mice with obesity induced by a high-fat (HF) diet. Therefore, we investigated the influence of DCA on the functions of vascular smooth muscle cells (VSMCs) because the initiation and progression of atherosclerosis are associated with VSMC proliferation and migration. DCA induced c-jun N-terminal kinase (JNK) activation whereas a JNK inhibitor prevented DCA-induced VSMC proliferation and migration. Based on these findings, we examined whether DCA promotes the expression of platelet-derived growth factor β-receptor (PDGFRβ) that has a c-Jun binding site in its promoter region. The mRNA and protein expression levels of PDGFRβ were upregulated in VSMCs after a 24- and 48-h incubation with DCA, respectively. The effects of PDGF such as proliferation and migration of VSMCs were promoted after a 48-h incubation with DCA despite the absence of DCA during PDGF stimulation. These findings suggest that elevated serum concentrations of DCA are involved in the pathogenesis of atherosclerosis in HF-induced obesity. |
| doi_str_mv | 10.3177/jnsv.60.450 |
| format | Article |
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Serum levels of the bile acid deoxycholic acid (DCA) are elevated in mice with obesity induced by a high-fat (HF) diet. Therefore, we investigated the influence of DCA on the functions of vascular smooth muscle cells (VSMCs) because the initiation and progression of atherosclerosis are associated with VSMC proliferation and migration. DCA induced c-jun N-terminal kinase (JNK) activation whereas a JNK inhibitor prevented DCA-induced VSMC proliferation and migration. Based on these findings, we examined whether DCA promotes the expression of platelet-derived growth factor β-receptor (PDGFRβ) that has a c-Jun binding site in its promoter region. The mRNA and protein expression levels of PDGFRβ were upregulated in VSMCs after a 24- and 48-h incubation with DCA, respectively. The effects of PDGF such as proliferation and migration of VSMCs were promoted after a 48-h incubation with DCA despite the absence of DCA during PDGF stimulation. These findings suggest that elevated serum concentrations of DCA are involved in the pathogenesis of atherosclerosis in HF-induced obesity.</description><identifier>ISSN: 0301-4800</identifier><identifier>EISSN: 1881-7742</identifier><identifier>DOI: 10.3177/jnsv.60.450</identifier><identifier>PMID: 25866311</identifier><language>eng</language><publisher>Japan: Center for Academic Publications Japan</publisher><subject>Animals ; atherosclerosis ; Atherosclerosis - etiology ; Atherosclerosis - pathology ; bile acid ; Binding Sites ; Cell Movement - drug effects ; Cell Proliferation - drug effects ; Cells, Cultured ; Deoxycholic Acid - adverse effects ; enterobacterium ; high-fat diet ; JNK Mitogen-Activated Protein Kinases - genetics ; JNK Mitogen-Activated Protein Kinases - metabolism ; Muscle, Smooth, Vascular - cytology ; Muscle, Smooth, Vascular - drug effects ; Myocytes, Smooth Muscle - drug effects ; Myocytes, Smooth Muscle - metabolism ; Promoter Regions, Genetic ; Rats ; Rats, Sprague-Dawley ; Receptor, Platelet-Derived Growth Factor beta - genetics ; Receptor, Platelet-Derived Growth Factor beta - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Up-Regulation</subject><ispartof>Journal of Nutritional Science and Vitaminology, 2014, Vol.60(6), pp.450-454</ispartof><rights>2014 by the Center for Academic Publications Japan</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c555t-27bfe50a56bf615730cf4c152952593a3fa432947f72f710ec3882b96fed46933</citedby><cites>FETCH-LOGICAL-c555t-27bfe50a56bf615730cf4c152952593a3fa432947f72f710ec3882b96fed46933</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1877,4010,27900,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25866311$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SHIMIZU, Hidehisa</creatorcontrib><creatorcontrib>HAGIO, Masahito</creatorcontrib><creatorcontrib>IWAYA, Hitoshi</creatorcontrib><creatorcontrib>TSUNEKI, Ikuya</creatorcontrib><creatorcontrib>LEE, Ja-Young</creatorcontrib><creatorcontrib>FUKIYA, Satoru</creatorcontrib><creatorcontrib>YOKOTA, Atsushi</creatorcontrib><creatorcontrib>MIYAZAKI, Hitoshi</creatorcontrib><creatorcontrib>HARA, Hiroshi</creatorcontrib><creatorcontrib>ISHIZUKA, Satoshi</creatorcontrib><title>Deoxycholic Acid Is Involved in the Proliferation and Migration of Vascular Smooth Muscle Cells</title><title>Journal of Nutritional Science and Vitaminology</title><addtitle>J Nutr Sci Vitaminol</addtitle><description>Obesity is increasingly becoming associated with increased risk of atherosclerosis. Serum levels of the bile acid deoxycholic acid (DCA) are elevated in mice with obesity induced by a high-fat (HF) diet. Therefore, we investigated the influence of DCA on the functions of vascular smooth muscle cells (VSMCs) because the initiation and progression of atherosclerosis are associated with VSMC proliferation and migration. DCA induced c-jun N-terminal kinase (JNK) activation whereas a JNK inhibitor prevented DCA-induced VSMC proliferation and migration. Based on these findings, we examined whether DCA promotes the expression of platelet-derived growth factor β-receptor (PDGFRβ) that has a c-Jun binding site in its promoter region. The mRNA and protein expression levels of PDGFRβ were upregulated in VSMCs after a 24- and 48-h incubation with DCA, respectively. The effects of PDGF such as proliferation and migration of VSMCs were promoted after a 48-h incubation with DCA despite the absence of DCA during PDGF stimulation. These findings suggest that elevated serum concentrations of DCA are involved in the pathogenesis of atherosclerosis in HF-induced obesity.</description><subject>Animals</subject><subject>atherosclerosis</subject><subject>Atherosclerosis - etiology</subject><subject>Atherosclerosis - pathology</subject><subject>bile acid</subject><subject>Binding Sites</subject><subject>Cell Movement - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Cells, Cultured</subject><subject>Deoxycholic Acid - adverse effects</subject><subject>enterobacterium</subject><subject>high-fat diet</subject><subject>JNK Mitogen-Activated Protein Kinases - genetics</subject><subject>JNK Mitogen-Activated Protein Kinases - metabolism</subject><subject>Muscle, Smooth, Vascular - cytology</subject><subject>Muscle, Smooth, Vascular - drug effects</subject><subject>Myocytes, Smooth Muscle - drug effects</subject><subject>Myocytes, Smooth Muscle - metabolism</subject><subject>Promoter Regions, Genetic</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptor, Platelet-Derived Growth Factor beta - genetics</subject><subject>Receptor, Platelet-Derived Growth Factor beta - metabolism</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Up-Regulation</subject><issn>0301-4800</issn><issn>1881-7742</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kFtrwjAYhsPYmM7tavcj96Mu56Q3A3EnQdlgh9uSpomt1EaSKvPfr6Lr1cfL-_DC9wBwi9GYYikfVk3cjQUaM47OwBArhRMpGTkHQ0QRTphCaACuYlwhxFLF1CUYEK6EoBgPQfZk_e_elL6uDJyYqoCzCGfNztc7W8CqgW1p4UfoameDbivfQN0UcFEtT8k7-KOj2dY6wM-1920JF9toaguntq7jNbhwuo725nRH4Pvl-Wv6lszfX2fTyTwxnPM2ITJ3liPNRe4E5pIi45jBnKSc8JRq6jSjJGXSSeIkRtZQpUieCmcLJlJKR-D-uGuCjzFYl21CtdZhn2GUHTRlB02ZQFmnqaPvjvRmm69t0bP_Xjrg8QisYquXtgd0aKvut35MnBb7wpQ6ZLahf6m1em4</recordid><startdate>2014</startdate><enddate>2014</enddate><creator>SHIMIZU, Hidehisa</creator><creator>HAGIO, Masahito</creator><creator>IWAYA, Hitoshi</creator><creator>TSUNEKI, Ikuya</creator><creator>LEE, Ja-Young</creator><creator>FUKIYA, Satoru</creator><creator>YOKOTA, Atsushi</creator><creator>MIYAZAKI, Hitoshi</creator><creator>HARA, Hiroshi</creator><creator>ISHIZUKA, Satoshi</creator><general>Center for Academic Publications Japan</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></search><sort><creationdate>2014</creationdate><title>Deoxycholic Acid Is Involved in the Proliferation and Migration of Vascular Smooth Muscle Cells</title><author>SHIMIZU, Hidehisa ; HAGIO, Masahito ; IWAYA, Hitoshi ; TSUNEKI, Ikuya ; LEE, Ja-Young ; FUKIYA, Satoru ; YOKOTA, Atsushi ; MIYAZAKI, Hitoshi ; HARA, Hiroshi ; ISHIZUKA, Satoshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c555t-27bfe50a56bf615730cf4c152952593a3fa432947f72f710ec3882b96fed46933</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>atherosclerosis</topic><topic>Atherosclerosis - etiology</topic><topic>Atherosclerosis - pathology</topic><topic>bile acid</topic><topic>Binding Sites</topic><topic>Cell Movement - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>Cells, Cultured</topic><topic>Deoxycholic Acid - adverse effects</topic><topic>enterobacterium</topic><topic>high-fat diet</topic><topic>JNK Mitogen-Activated Protein Kinases - genetics</topic><topic>JNK Mitogen-Activated Protein Kinases - metabolism</topic><topic>Muscle, Smooth, Vascular - cytology</topic><topic>Muscle, Smooth, Vascular - drug effects</topic><topic>Myocytes, Smooth Muscle - drug effects</topic><topic>Myocytes, Smooth Muscle - metabolism</topic><topic>Promoter Regions, Genetic</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptor, Platelet-Derived Growth Factor beta - genetics</topic><topic>Receptor, Platelet-Derived Growth Factor beta - metabolism</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SHIMIZU, Hidehisa</creatorcontrib><creatorcontrib>HAGIO, Masahito</creatorcontrib><creatorcontrib>IWAYA, Hitoshi</creatorcontrib><creatorcontrib>TSUNEKI, Ikuya</creatorcontrib><creatorcontrib>LEE, Ja-Young</creatorcontrib><creatorcontrib>FUKIYA, Satoru</creatorcontrib><creatorcontrib>YOKOTA, Atsushi</creatorcontrib><creatorcontrib>MIYAZAKI, Hitoshi</creatorcontrib><creatorcontrib>HARA, Hiroshi</creatorcontrib><creatorcontrib>ISHIZUKA, Satoshi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of Nutritional Science and Vitaminology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SHIMIZU, Hidehisa</au><au>HAGIO, Masahito</au><au>IWAYA, Hitoshi</au><au>TSUNEKI, Ikuya</au><au>LEE, Ja-Young</au><au>FUKIYA, Satoru</au><au>YOKOTA, Atsushi</au><au>MIYAZAKI, Hitoshi</au><au>HARA, Hiroshi</au><au>ISHIZUKA, Satoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Deoxycholic Acid Is Involved in the Proliferation and Migration of Vascular Smooth Muscle Cells</atitle><jtitle>Journal of Nutritional Science and Vitaminology</jtitle><addtitle>J Nutr Sci Vitaminol</addtitle><date>2014</date><risdate>2014</risdate><volume>60</volume><issue>6</issue><spage>450</spage><epage>454</epage><pages>450-454</pages><issn>0301-4800</issn><eissn>1881-7742</eissn><abstract>Obesity is increasingly becoming associated with increased risk of atherosclerosis. Serum levels of the bile acid deoxycholic acid (DCA) are elevated in mice with obesity induced by a high-fat (HF) diet. Therefore, we investigated the influence of DCA on the functions of vascular smooth muscle cells (VSMCs) because the initiation and progression of atherosclerosis are associated with VSMC proliferation and migration. DCA induced c-jun N-terminal kinase (JNK) activation whereas a JNK inhibitor prevented DCA-induced VSMC proliferation and migration. Based on these findings, we examined whether DCA promotes the expression of platelet-derived growth factor β-receptor (PDGFRβ) that has a c-Jun binding site in its promoter region. The mRNA and protein expression levels of PDGFRβ were upregulated in VSMCs after a 24- and 48-h incubation with DCA, respectively. The effects of PDGF such as proliferation and migration of VSMCs were promoted after a 48-h incubation with DCA despite the absence of DCA during PDGF stimulation. These findings suggest that elevated serum concentrations of DCA are involved in the pathogenesis of atherosclerosis in HF-induced obesity.</abstract><cop>Japan</cop><pub>Center for Academic Publications Japan</pub><pmid>25866311</pmid><doi>10.3177/jnsv.60.450</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals atherosclerosis Atherosclerosis - etiology Atherosclerosis - pathology bile acid Binding Sites Cell Movement - drug effects Cell Proliferation - drug effects Cells, Cultured Deoxycholic Acid - adverse effects enterobacterium high-fat diet JNK Mitogen-Activated Protein Kinases - genetics JNK Mitogen-Activated Protein Kinases - metabolism Muscle, Smooth, Vascular - cytology Muscle, Smooth, Vascular - drug effects Myocytes, Smooth Muscle - drug effects Myocytes, Smooth Muscle - metabolism Promoter Regions, Genetic Rats Rats, Sprague-Dawley Receptor, Platelet-Derived Growth Factor beta - genetics Receptor, Platelet-Derived Growth Factor beta - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism Up-Regulation |
| title | Deoxycholic Acid Is Involved in the Proliferation and Migration of Vascular Smooth Muscle Cells |
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