Clusterin/apolipoprotein J attenuates angiotensin II-induced renal fibrosis
The blockade of angiotensin II (Ang II) is a major therapeutic strategy for diabetic nephropathy. The main roles of Ang II in renal disease are mediated via the Ang type 1 receptor (AT1R). Upregulation of clusterin/apolipoprotein J has been reported in nephropathy models, suggesting it has a protect...
Gespeichert in:
| Veröffentlicht in: | PloS one 2014-08, Vol.9 (8), p.e105635-e105635 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e105635 |
|---|---|
| container_issue | 8 |
| container_start_page | e105635 |
| container_title | PloS one |
| container_volume | 9 |
| creator | Jung, Gwon-Soo Jeon, Jae-Han Jung, Yun-A Choi, Yeon-Kyung Kim, Hye-Soon Kim, Jung-Guk Park, Keun-Gyu Kim, Mi-Kyung Lee, In-Kyu |
| description | The blockade of angiotensin II (Ang II) is a major therapeutic strategy for diabetic nephropathy. The main roles of Ang II in renal disease are mediated via the Ang type 1 receptor (AT1R). Upregulation of clusterin/apolipoprotein J has been reported in nephropathy models, suggesting it has a protective role in nephropathogenesis. Here, we studied how clusterin acts against Ang II-induced renal fibrosis. Levels of AT1R and fibrotic markers in clusterin-/- mice and Ang II infused rats transfected with an adenovirus encoding clusterin were evaluated by immunoblot analysis, real time RT-PCR, and immunohistochemical staining. The effect of clusterin on renal fibrosis was evaluated in NRK-52E cells, a cultured renal tubular epithelial cell line, using immunoblot analysis and real time RT-PCR. Nuclear localization of NF-κB was evaluated using immunofluorecence and co-immunoprecipitation. Renal fibrosis and expression of AT1R was higher in the kidneys of clusterin-/- mice than in those of wild-type mice. Furthermore, loss of clusterin accelerated Ang II-stimulated renal fibrosis and AT1R expression. Overexpression of clusterin in proximal tubular epithelial cells decreased the levels of Ang II-stimulated fibrotic markers and AT1R. Moreover, intrarenal delivery of clusterin attenuated Ang II-mediated expression of fibrotic markers and AT1R in rats. Fluorescence microscopy and co-immunoprecipitation in conjunction with western blot revealed that clusterin inhibited Ang II-stimulated nuclear localization of p-NF-κB via a direct physical interaction and subsequently decreased the AT1R level in proximal tubular epithelial cells. These data suggest that clusterin attenuates Ang II-induced renal fibrosis by inhibition of NF-κB activation and subsequent downregulation of AT1R. This study raises the possibility that clusterin could be used as a therapeutic target for Ang II-induced renal diseases. |
| doi_str_mv | 10.1371/journal.pone.0105635 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1555403738</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A418126925</galeid><doaj_id>oai_doaj_org_article_f52f72a716604e119e5854a8a07a792d</doaj_id><sourcerecordid>A418126925</sourcerecordid><originalsourceid>FETCH-LOGICAL-c692t-cbfb37bfa4fbca8cf599c52739b84602412d1086e4a8b3835fd86e59ad04ca53</originalsourceid><addsrcrecordid>eNqNkl1v0zAUhiMEYlvhHyCohDTBRTt_xPm4QZoqPgqTJsHErXXi2K0r185sB8G_x1mzqUG7QLlIfPy877FP3ix7hdES0xJf7FzvLZhl56xcIoxYQdmT7BTXlCwKgujTo--T7CyEHUKMVkXxPDshDOcVw_g0-7YyfYjSa3sBnTO6c513UWo7_zqHGKXtIcowB7vRqWxD2livF9q2vZDt3Mt0grnSjXdBhxfZMwUmyJfje5bdfPp4s_qyuLr-vF5dXi1EUZO4EI1qaNkoyFUjoBKK1bVgpKR1U-UFIjkmLUZVIXOoGlpRptq0YDW0KBfA6Cx7c7DtjAt8HEPgmDGWI1omxSxbH4jWwY53Xu_B_-EONL8rOL_h4KMWRnLFiCoJlLgoUC4xriWrWGoMqISyJm3y-jB265u9bIW00YOZmE53rN7yjfvFc5zjCqNk8G408O62lyHyvQ5CGgNWuv7u3AWpSloO6Nt_0MdvN1IbSBfQVrnUVwym_HJoSdKUhyktH6HS08q9FikzSqf6RPB-IkhMlL_jBvoQ-PrH9_9nr39O2fMjdivBxG1wpo_a2TAF8wMoUpqCl-phyBjxIfL30-BD5PkY-SR7ffyDHkT3Gad_AaLW-z4</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1555403738</pqid></control><display><type>article</type><title>Clusterin/apolipoprotein J attenuates angiotensin II-induced renal fibrosis</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Jung, Gwon-Soo ; Jeon, Jae-Han ; Jung, Yun-A ; Choi, Yeon-Kyung ; Kim, Hye-Soon ; Kim, Jung-Guk ; Park, Keun-Gyu ; Kim, Mi-Kyung ; Lee, In-Kyu</creator><contributor>Ashton, Nick</contributor><creatorcontrib>Jung, Gwon-Soo ; Jeon, Jae-Han ; Jung, Yun-A ; Choi, Yeon-Kyung ; Kim, Hye-Soon ; Kim, Jung-Guk ; Park, Keun-Gyu ; Kim, Mi-Kyung ; Lee, In-Kyu ; Ashton, Nick</creatorcontrib><description>The blockade of angiotensin II (Ang II) is a major therapeutic strategy for diabetic nephropathy. The main roles of Ang II in renal disease are mediated via the Ang type 1 receptor (AT1R). Upregulation of clusterin/apolipoprotein J has been reported in nephropathy models, suggesting it has a protective role in nephropathogenesis. Here, we studied how clusterin acts against Ang II-induced renal fibrosis. Levels of AT1R and fibrotic markers in clusterin-/- mice and Ang II infused rats transfected with an adenovirus encoding clusterin were evaluated by immunoblot analysis, real time RT-PCR, and immunohistochemical staining. The effect of clusterin on renal fibrosis was evaluated in NRK-52E cells, a cultured renal tubular epithelial cell line, using immunoblot analysis and real time RT-PCR. Nuclear localization of NF-κB was evaluated using immunofluorecence and co-immunoprecipitation. Renal fibrosis and expression of AT1R was higher in the kidneys of clusterin-/- mice than in those of wild-type mice. Furthermore, loss of clusterin accelerated Ang II-stimulated renal fibrosis and AT1R expression. Overexpression of clusterin in proximal tubular epithelial cells decreased the levels of Ang II-stimulated fibrotic markers and AT1R. Moreover, intrarenal delivery of clusterin attenuated Ang II-mediated expression of fibrotic markers and AT1R in rats. Fluorescence microscopy and co-immunoprecipitation in conjunction with western blot revealed that clusterin inhibited Ang II-stimulated nuclear localization of p-NF-κB via a direct physical interaction and subsequently decreased the AT1R level in proximal tubular epithelial cells. These data suggest that clusterin attenuates Ang II-induced renal fibrosis by inhibition of NF-κB activation and subsequent downregulation of AT1R. This study raises the possibility that clusterin could be used as a therapeutic target for Ang II-induced renal diseases.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0105635</identifier><identifier>PMID: 25148511</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenoviruses ; Angiotensin ; Angiotensin II ; Angiotensin II - genetics ; Angiotensin II - metabolism ; Angiotensins ; Animal models ; Animals ; Apolipoproteins ; Apoptosis ; Attenuation ; Biology and Life Sciences ; Clusterin ; Clusterin - genetics ; Clusterin - metabolism ; Collagen ; Diabetes ; Diabetes mellitus ; Diabetic nephropathies ; Diabetic nephropathy ; Endocrinology ; Epithelial cells ; Fibrosis ; Fibrosis - genetics ; Fibrosis - metabolism ; Fibrosis - pathology ; Fluorescence ; Fluorescence microscopy ; Growth factors ; Health aspects ; Humans ; Hypertension ; Immunoglobulins ; Immunohistochemistry ; Immunoprecipitation ; Infections ; Inflammation ; Internal medicine ; Kidney diseases ; Kidney Diseases - genetics ; Kidney Diseases - metabolism ; Kidney Diseases - pathology ; Kidneys ; Localization ; Male ; Markers ; Medicine ; Medicine and Health Sciences ; Metabolism ; Mice ; Mice, Knockout ; Nephropathy ; NF-κB protein ; Polymerase chain reaction ; Proteins ; Rats ; Rats, Sprague-Dawley ; Real time ; Receptor, Angiotensin, Type 1 - genetics ; Receptor, Angiotensin, Type 1 - metabolism ; Rodents ; Signal transduction ; Therapeutic applications ; Transcription factors</subject><ispartof>PloS one, 2014-08, Vol.9 (8), p.e105635-e105635</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Jung et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Jung et al 2014 Jung et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-cbfb37bfa4fbca8cf599c52739b84602412d1086e4a8b3835fd86e59ad04ca53</citedby><cites>FETCH-LOGICAL-c692t-cbfb37bfa4fbca8cf599c52739b84602412d1086e4a8b3835fd86e59ad04ca53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4141810/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4141810/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23868,27926,27927,53793,53795</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25148511$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Ashton, Nick</contributor><creatorcontrib>Jung, Gwon-Soo</creatorcontrib><creatorcontrib>Jeon, Jae-Han</creatorcontrib><creatorcontrib>Jung, Yun-A</creatorcontrib><creatorcontrib>Choi, Yeon-Kyung</creatorcontrib><creatorcontrib>Kim, Hye-Soon</creatorcontrib><creatorcontrib>Kim, Jung-Guk</creatorcontrib><creatorcontrib>Park, Keun-Gyu</creatorcontrib><creatorcontrib>Kim, Mi-Kyung</creatorcontrib><creatorcontrib>Lee, In-Kyu</creatorcontrib><title>Clusterin/apolipoprotein J attenuates angiotensin II-induced renal fibrosis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The blockade of angiotensin II (Ang II) is a major therapeutic strategy for diabetic nephropathy. The main roles of Ang II in renal disease are mediated via the Ang type 1 receptor (AT1R). Upregulation of clusterin/apolipoprotein J has been reported in nephropathy models, suggesting it has a protective role in nephropathogenesis. Here, we studied how clusterin acts against Ang II-induced renal fibrosis. Levels of AT1R and fibrotic markers in clusterin-/- mice and Ang II infused rats transfected with an adenovirus encoding clusterin were evaluated by immunoblot analysis, real time RT-PCR, and immunohistochemical staining. The effect of clusterin on renal fibrosis was evaluated in NRK-52E cells, a cultured renal tubular epithelial cell line, using immunoblot analysis and real time RT-PCR. Nuclear localization of NF-κB was evaluated using immunofluorecence and co-immunoprecipitation. Renal fibrosis and expression of AT1R was higher in the kidneys of clusterin-/- mice than in those of wild-type mice. Furthermore, loss of clusterin accelerated Ang II-stimulated renal fibrosis and AT1R expression. Overexpression of clusterin in proximal tubular epithelial cells decreased the levels of Ang II-stimulated fibrotic markers and AT1R. Moreover, intrarenal delivery of clusterin attenuated Ang II-mediated expression of fibrotic markers and AT1R in rats. Fluorescence microscopy and co-immunoprecipitation in conjunction with western blot revealed that clusterin inhibited Ang II-stimulated nuclear localization of p-NF-κB via a direct physical interaction and subsequently decreased the AT1R level in proximal tubular epithelial cells. These data suggest that clusterin attenuates Ang II-induced renal fibrosis by inhibition of NF-κB activation and subsequent downregulation of AT1R. This study raises the possibility that clusterin could be used as a therapeutic target for Ang II-induced renal diseases.</description><subject>Adenoviruses</subject><subject>Angiotensin</subject><subject>Angiotensin II</subject><subject>Angiotensin II - genetics</subject><subject>Angiotensin II - metabolism</subject><subject>Angiotensins</subject><subject>Animal models</subject><subject>Animals</subject><subject>Apolipoproteins</subject><subject>Apoptosis</subject><subject>Attenuation</subject><subject>Biology and Life Sciences</subject><subject>Clusterin</subject><subject>Clusterin - genetics</subject><subject>Clusterin - metabolism</subject><subject>Collagen</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetic nephropathies</subject><subject>Diabetic nephropathy</subject><subject>Endocrinology</subject><subject>Epithelial cells</subject><subject>Fibrosis</subject><subject>Fibrosis - genetics</subject><subject>Fibrosis - metabolism</subject><subject>Fibrosis - pathology</subject><subject>Fluorescence</subject><subject>Fluorescence microscopy</subject><subject>Growth factors</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Immunoglobulins</subject><subject>Immunohistochemistry</subject><subject>Immunoprecipitation</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Internal medicine</subject><subject>Kidney diseases</subject><subject>Kidney Diseases - genetics</subject><subject>Kidney Diseases - metabolism</subject><subject>Kidney Diseases - pathology</subject><subject>Kidneys</subject><subject>Localization</subject><subject>Male</subject><subject>Markers</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Nephropathy</subject><subject>NF-κB protein</subject><subject>Polymerase chain reaction</subject><subject>Proteins</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Real time</subject><subject>Receptor, Angiotensin, Type 1 - genetics</subject><subject>Receptor, Angiotensin, Type 1 - metabolism</subject><subject>Rodents</subject><subject>Signal transduction</subject><subject>Therapeutic applications</subject><subject>Transcription factors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl1v0zAUhiMEYlvhHyCohDTBRTt_xPm4QZoqPgqTJsHErXXi2K0r185sB8G_x1mzqUG7QLlIfPy877FP3ix7hdES0xJf7FzvLZhl56xcIoxYQdmT7BTXlCwKgujTo--T7CyEHUKMVkXxPDshDOcVw_g0-7YyfYjSa3sBnTO6c513UWo7_zqHGKXtIcowB7vRqWxD2livF9q2vZDt3Mt0grnSjXdBhxfZMwUmyJfje5bdfPp4s_qyuLr-vF5dXi1EUZO4EI1qaNkoyFUjoBKK1bVgpKR1U-UFIjkmLUZVIXOoGlpRptq0YDW0KBfA6Cx7c7DtjAt8HEPgmDGWI1omxSxbH4jWwY53Xu_B_-EONL8rOL_h4KMWRnLFiCoJlLgoUC4xriWrWGoMqISyJm3y-jB265u9bIW00YOZmE53rN7yjfvFc5zjCqNk8G408O62lyHyvQ5CGgNWuv7u3AWpSloO6Nt_0MdvN1IbSBfQVrnUVwym_HJoSdKUhyktH6HS08q9FikzSqf6RPB-IkhMlL_jBvoQ-PrH9_9nr39O2fMjdivBxG1wpo_a2TAF8wMoUpqCl-phyBjxIfL30-BD5PkY-SR7ffyDHkT3Gad_AaLW-z4</recordid><startdate>20140822</startdate><enddate>20140822</enddate><creator>Jung, Gwon-Soo</creator><creator>Jeon, Jae-Han</creator><creator>Jung, Yun-A</creator><creator>Choi, Yeon-Kyung</creator><creator>Kim, Hye-Soon</creator><creator>Kim, Jung-Guk</creator><creator>Park, Keun-Gyu</creator><creator>Kim, Mi-Kyung</creator><creator>Lee, In-Kyu</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140822</creationdate><title>Clusterin/apolipoprotein J attenuates angiotensin II-induced renal fibrosis</title><author>Jung, Gwon-Soo ; Jeon, Jae-Han ; Jung, Yun-A ; Choi, Yeon-Kyung ; Kim, Hye-Soon ; Kim, Jung-Guk ; Park, Keun-Gyu ; Kim, Mi-Kyung ; Lee, In-Kyu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-cbfb37bfa4fbca8cf599c52739b84602412d1086e4a8b3835fd86e59ad04ca53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adenoviruses</topic><topic>Angiotensin</topic><topic>Angiotensin II</topic><topic>Angiotensin II - genetics</topic><topic>Angiotensin II - metabolism</topic><topic>Angiotensins</topic><topic>Animal models</topic><topic>Animals</topic><topic>Apolipoproteins</topic><topic>Apoptosis</topic><topic>Attenuation</topic><topic>Biology and Life Sciences</topic><topic>Clusterin</topic><topic>Clusterin - genetics</topic><topic>Clusterin - metabolism</topic><topic>Collagen</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetic nephropathies</topic><topic>Diabetic nephropathy</topic><topic>Endocrinology</topic><topic>Epithelial cells</topic><topic>Fibrosis</topic><topic>Fibrosis - genetics</topic><topic>Fibrosis - metabolism</topic><topic>Fibrosis - pathology</topic><topic>Fluorescence</topic><topic>Fluorescence microscopy</topic><topic>Growth factors</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Immunoglobulins</topic><topic>Immunohistochemistry</topic><topic>Immunoprecipitation</topic><topic>Infections</topic><topic>Inflammation</topic><topic>Internal medicine</topic><topic>Kidney diseases</topic><topic>Kidney Diseases - genetics</topic><topic>Kidney Diseases - metabolism</topic><topic>Kidney Diseases - pathology</topic><topic>Kidneys</topic><topic>Localization</topic><topic>Male</topic><topic>Markers</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Nephropathy</topic><topic>NF-κB protein</topic><topic>Polymerase chain reaction</topic><topic>Proteins</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Real time</topic><topic>Receptor, Angiotensin, Type 1 - genetics</topic><topic>Receptor, Angiotensin, Type 1 - metabolism</topic><topic>Rodents</topic><topic>Signal transduction</topic><topic>Therapeutic applications</topic><topic>Transcription factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jung, Gwon-Soo</creatorcontrib><creatorcontrib>Jeon, Jae-Han</creatorcontrib><creatorcontrib>Jung, Yun-A</creatorcontrib><creatorcontrib>Choi, Yeon-Kyung</creatorcontrib><creatorcontrib>Kim, Hye-Soon</creatorcontrib><creatorcontrib>Kim, Jung-Guk</creatorcontrib><creatorcontrib>Park, Keun-Gyu</creatorcontrib><creatorcontrib>Kim, Mi-Kyung</creatorcontrib><creatorcontrib>Lee, In-Kyu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jung, Gwon-Soo</au><au>Jeon, Jae-Han</au><au>Jung, Yun-A</au><au>Choi, Yeon-Kyung</au><au>Kim, Hye-Soon</au><au>Kim, Jung-Guk</au><au>Park, Keun-Gyu</au><au>Kim, Mi-Kyung</au><au>Lee, In-Kyu</au><au>Ashton, Nick</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clusterin/apolipoprotein J attenuates angiotensin II-induced renal fibrosis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-08-22</date><risdate>2014</risdate><volume>9</volume><issue>8</issue><spage>e105635</spage><epage>e105635</epage><pages>e105635-e105635</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The blockade of angiotensin II (Ang II) is a major therapeutic strategy for diabetic nephropathy. The main roles of Ang II in renal disease are mediated via the Ang type 1 receptor (AT1R). Upregulation of clusterin/apolipoprotein J has been reported in nephropathy models, suggesting it has a protective role in nephropathogenesis. Here, we studied how clusterin acts against Ang II-induced renal fibrosis. Levels of AT1R and fibrotic markers in clusterin-/- mice and Ang II infused rats transfected with an adenovirus encoding clusterin were evaluated by immunoblot analysis, real time RT-PCR, and immunohistochemical staining. The effect of clusterin on renal fibrosis was evaluated in NRK-52E cells, a cultured renal tubular epithelial cell line, using immunoblot analysis and real time RT-PCR. Nuclear localization of NF-κB was evaluated using immunofluorecence and co-immunoprecipitation. Renal fibrosis and expression of AT1R was higher in the kidneys of clusterin-/- mice than in those of wild-type mice. Furthermore, loss of clusterin accelerated Ang II-stimulated renal fibrosis and AT1R expression. Overexpression of clusterin in proximal tubular epithelial cells decreased the levels of Ang II-stimulated fibrotic markers and AT1R. Moreover, intrarenal delivery of clusterin attenuated Ang II-mediated expression of fibrotic markers and AT1R in rats. Fluorescence microscopy and co-immunoprecipitation in conjunction with western blot revealed that clusterin inhibited Ang II-stimulated nuclear localization of p-NF-κB via a direct physical interaction and subsequently decreased the AT1R level in proximal tubular epithelial cells. These data suggest that clusterin attenuates Ang II-induced renal fibrosis by inhibition of NF-κB activation and subsequent downregulation of AT1R. This study raises the possibility that clusterin could be used as a therapeutic target for Ang II-induced renal diseases.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25148511</pmid><doi>10.1371/journal.pone.0105635</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-08, Vol.9 (8), p.e105635-e105635 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1555403738 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adenoviruses Angiotensin Angiotensin II Angiotensin II - genetics Angiotensin II - metabolism Angiotensins Animal models Animals Apolipoproteins Apoptosis Attenuation Biology and Life Sciences Clusterin Clusterin - genetics Clusterin - metabolism Collagen Diabetes Diabetes mellitus Diabetic nephropathies Diabetic nephropathy Endocrinology Epithelial cells Fibrosis Fibrosis - genetics Fibrosis - metabolism Fibrosis - pathology Fluorescence Fluorescence microscopy Growth factors Health aspects Humans Hypertension Immunoglobulins Immunohistochemistry Immunoprecipitation Infections Inflammation Internal medicine Kidney diseases Kidney Diseases - genetics Kidney Diseases - metabolism Kidney Diseases - pathology Kidneys Localization Male Markers Medicine Medicine and Health Sciences Metabolism Mice Mice, Knockout Nephropathy NF-κB protein Polymerase chain reaction Proteins Rats Rats, Sprague-Dawley Real time Receptor, Angiotensin, Type 1 - genetics Receptor, Angiotensin, Type 1 - metabolism Rodents Signal transduction Therapeutic applications Transcription factors |
| title | Clusterin/apolipoprotein J attenuates angiotensin II-induced renal fibrosis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-18T12%3A24%3A15IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Clusterin/apolipoprotein%20J%20attenuates%20angiotensin%20II-induced%20renal%20fibrosis&rft.jtitle=PloS%20one&rft.au=Jung,%20Gwon-Soo&rft.date=2014-08-22&rft.volume=9&rft.issue=8&rft.spage=e105635&rft.epage=e105635&rft.pages=e105635-e105635&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0105635&rft_dat=%3Cgale_plos_%3EA418126925%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1555403738&rft_id=info:pmid/25148511&rft_galeid=A418126925&rft_doaj_id=oai_doaj_org_article_f52f72a716604e119e5854a8a07a792d&rfr_iscdi=true |