In vivo delivery of small interfering RNA targeting brain capillary endothelial cells
Brain capillary endothelial cells (BCECs) play an important role in blood–brain barrier (BBB) functions and pathophysiologic mechanisms in brain ischemia and inflammation. We try to suppress gene expression in BCECs by intravenous application of small interfering RNA (siRNA). After injection of larg...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2006-02, Vol.340 (1), p.263-267 |
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| creator | Hino, Taro Yokota, Takanori Ito, Shingo Nishina, Kazutaka Kang, Young-Sook Mori, Shinobu Hori, Satoko Kanda, Takashi Terasaki, Tetsuya Mizusawa, Hidehiro |
| description | Brain capillary endothelial cells (BCECs) play an important role in blood–brain barrier (BBB) functions and pathophysiologic mechanisms in brain ischemia and inflammation. We try to suppress gene expression in BCECs by intravenous application of small interfering RNA (siRNA). After injection of large dose siRNA with hydrodynamic technique to mouse, suppression of endogenous protein and the BBB function of BCECs was investigated. The brain-to-blood transport function of organic anion transporter 3 (OAT3) that expressed in BCECs was evaluated by Brain Efflux Index method in mouse. The siRNA could be delivered to BCECs and efficiently inhibited endogenously expressed protein of BCECs. The suppression effect of siRNA to OAT3 is enough to reduce the brain-to-blood transport of OAT3 substrate, benzylpenicillin at BBB. The in vivo siRNA-silencing method with hydrodynamic technique may be useful for the study of BBB function and gene therapy targeting BCECs. |
| doi_str_mv | 10.1016/j.bbrc.2005.11.173 |
| format | Article |
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We try to suppress gene expression in BCECs by intravenous application of small interfering RNA (siRNA). After injection of large dose siRNA with hydrodynamic technique to mouse, suppression of endogenous protein and the BBB function of BCECs was investigated. The brain-to-blood transport function of organic anion transporter 3 (OAT3) that expressed in BCECs was evaluated by Brain Efflux Index method in mouse. The siRNA could be delivered to BCECs and efficiently inhibited endogenously expressed protein of BCECs. The suppression effect of siRNA to OAT3 is enough to reduce the brain-to-blood transport of OAT3 substrate, benzylpenicillin at BBB. 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We try to suppress gene expression in BCECs by intravenous application of small interfering RNA (siRNA). After injection of large dose siRNA with hydrodynamic technique to mouse, suppression of endogenous protein and the BBB function of BCECs was investigated. The brain-to-blood transport function of organic anion transporter 3 (OAT3) that expressed in BCECs was evaluated by Brain Efflux Index method in mouse. The siRNA could be delivered to BCECs and efficiently inhibited endogenously expressed protein of BCECs. The suppression effect of siRNA to OAT3 is enough to reduce the brain-to-blood transport of OAT3 substrate, benzylpenicillin at BBB. The in vivo siRNA-silencing method with hydrodynamic technique may be useful for the study of BBB function and gene therapy targeting BCECs.</description><subject>Animals</subject><subject>Blood-Brain Barrier - physiology</subject><subject>Blood–brain barrier</subject><subject>Brain - blood supply</subject><subject>Brain - physiology</subject><subject>Brain inflammation</subject><subject>Brain ischemia</subject><subject>Cell Line</subject><subject>Drug delivery system</subject><subject>Drug Delivery Systems - methods</subject><subject>Endothelial Cells - physiology</subject><subject>Gene Silencing</subject><subject>Gene Targeting - methods</subject><subject>Humans</subject><subject>Kidney - physiology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred ICR</subject><subject>Organic anion transporter 3</subject><subject>Organic Anion Transporters, Sodium-Independent - genetics</subject><subject>Organic Anion Transporters, Sodium-Independent - metabolism</subject><subject>RNA, Small Interfering - administration & dosage</subject><subject>RNA, Small Interfering - genetics</subject><subject>Small interfering RNA</subject><subject>Superoxide Dismutase - genetics</subject><subject>Superoxide Dismutase - metabolism</subject><subject>Superoxide Dismutase-1</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkM1q3DAURkVpaaZpX6CLolV3du-VZcmCbkLoTyA0UBLITsjyVapBY08lz0DevjYz0F27EoLzHaTD2HuEGgHVp23d99nXAqCtEWvUzQu2QTBQCQT5km0AQFXC4OMFe1PKFgBRKvOaXaBqlBQtbNjDzciP8TjxgVI8Un7mU-Bl51LicZwpB8pxfOI_f1zx2eUnmtdbn10cuXf7mJJbJjQO0_xrEbjEPaVU3rJXwaVC787nJXv4-uX--nt1e_ft5vrqtvKyxbmS2kMbeh9M54XXnSENLgyhD04II2QjB-2k65uOJKHWnfSuUco0IMh3WjSX7OPJu8_T7wOV2e5iWV_gRpoOxSrddnoV_Q9EDdoooxdQnECfp1IyBbvPcbd80iLYtbrd2rW6XatbxGXZLKMPZ_uh39Hwd3LOvACfTwAtMY6Rsi0-0uhpiJn8bIcp_sv_B8fdk6E</recordid><startdate>20060203</startdate><enddate>20060203</enddate><creator>Hino, Taro</creator><creator>Yokota, Takanori</creator><creator>Ito, Shingo</creator><creator>Nishina, Kazutaka</creator><creator>Kang, Young-Sook</creator><creator>Mori, Shinobu</creator><creator>Hori, Satoko</creator><creator>Kanda, Takashi</creator><creator>Terasaki, Tetsuya</creator><creator>Mizusawa, Hidehiro</creator><general>Elsevier Inc</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><scope>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20060203</creationdate><title>In vivo delivery of small interfering RNA targeting brain capillary endothelial cells</title><author>Hino, Taro ; Yokota, Takanori ; Ito, Shingo ; Nishina, Kazutaka ; Kang, Young-Sook ; Mori, Shinobu ; Hori, Satoko ; Kanda, Takashi ; Terasaki, Tetsuya ; Mizusawa, Hidehiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-47c05fbcf98c2c789e70afdfbfa2292434d7a4ab38e4e17784ca3669302ec8723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Blood-Brain Barrier - physiology</topic><topic>Blood–brain barrier</topic><topic>Brain - blood supply</topic><topic>Brain - physiology</topic><topic>Brain inflammation</topic><topic>Brain ischemia</topic><topic>Cell Line</topic><topic>Drug delivery system</topic><topic>Drug Delivery Systems - methods</topic><topic>Endothelial Cells - physiology</topic><topic>Gene Silencing</topic><topic>Gene Targeting - methods</topic><topic>Humans</topic><topic>Kidney - physiology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred ICR</topic><topic>Organic anion transporter 3</topic><topic>Organic Anion Transporters, Sodium-Independent - genetics</topic><topic>Organic Anion Transporters, Sodium-Independent - metabolism</topic><topic>RNA, Small Interfering - administration & dosage</topic><topic>RNA, Small Interfering - genetics</topic><topic>Small interfering RNA</topic><topic>Superoxide Dismutase - genetics</topic><topic>Superoxide Dismutase - metabolism</topic><topic>Superoxide Dismutase-1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hino, Taro</creatorcontrib><creatorcontrib>Yokota, Takanori</creatorcontrib><creatorcontrib>Ito, Shingo</creatorcontrib><creatorcontrib>Nishina, Kazutaka</creatorcontrib><creatorcontrib>Kang, Young-Sook</creatorcontrib><creatorcontrib>Mori, Shinobu</creatorcontrib><creatorcontrib>Hori, Satoko</creatorcontrib><creatorcontrib>Kanda, Takashi</creatorcontrib><creatorcontrib>Terasaki, Tetsuya</creatorcontrib><creatorcontrib>Mizusawa, Hidehiro</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hino, Taro</au><au>Yokota, Takanori</au><au>Ito, Shingo</au><au>Nishina, Kazutaka</au><au>Kang, Young-Sook</au><au>Mori, Shinobu</au><au>Hori, Satoko</au><au>Kanda, Takashi</au><au>Terasaki, Tetsuya</au><au>Mizusawa, Hidehiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vivo delivery of small interfering RNA targeting brain capillary endothelial cells</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2006-02-03</date><risdate>2006</risdate><volume>340</volume><issue>1</issue><spage>263</spage><epage>267</epage><pages>263-267</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Brain capillary endothelial cells (BCECs) play an important role in blood–brain barrier (BBB) functions and pathophysiologic mechanisms in brain ischemia and inflammation. We try to suppress gene expression in BCECs by intravenous application of small interfering RNA (siRNA). After injection of large dose siRNA with hydrodynamic technique to mouse, suppression of endogenous protein and the BBB function of BCECs was investigated. The brain-to-blood transport function of organic anion transporter 3 (OAT3) that expressed in BCECs was evaluated by Brain Efflux Index method in mouse. The siRNA could be delivered to BCECs and efficiently inhibited endogenously expressed protein of BCECs. The suppression effect of siRNA to OAT3 is enough to reduce the brain-to-blood transport of OAT3 substrate, benzylpenicillin at BBB. The in vivo siRNA-silencing method with hydrodynamic technique may be useful for the study of BBB function and gene therapy targeting BCECs.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>16364250</pmid><doi>10.1016/j.bbrc.2005.11.173</doi><tpages>5</tpages></addata></record> |
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| subjects | Animals Blood-Brain Barrier - physiology Blood–brain barrier Brain - blood supply Brain - physiology Brain inflammation Brain ischemia Cell Line Drug delivery system Drug Delivery Systems - methods Endothelial Cells - physiology Gene Silencing Gene Targeting - methods Humans Kidney - physiology Male Mice Mice, Inbred ICR Organic anion transporter 3 Organic Anion Transporters, Sodium-Independent - genetics Organic Anion Transporters, Sodium-Independent - metabolism RNA, Small Interfering - administration & dosage RNA, Small Interfering - genetics Small interfering RNA Superoxide Dismutase - genetics Superoxide Dismutase - metabolism Superoxide Dismutase-1 |
| title | In vivo delivery of small interfering RNA targeting brain capillary endothelial cells |
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