IGFBP-5 Promotes Fibrosis Independently of Its Translocation to the Nucleus and Its Interaction with Nucleolin and IGF
Insulin-like growth factor binding protein (IGFBP)-5 levels are increased in systemic sclerosis (SSc) skin and lung. We previously reported that IGFBP-5 is a pro-fibrotic factor that induces extracellular matrix (ECM) production and deposition. Since IGFBP-5 contains a nuclear localization signal (N...
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| description | Insulin-like growth factor binding protein (IGFBP)-5 levels are increased in systemic sclerosis (SSc) skin and lung. We previously reported that IGFBP-5 is a pro-fibrotic factor that induces extracellular matrix (ECM) production and deposition. Since IGFBP-5 contains a nuclear localization signal (NLS) that facilitates its nuclear translocation, we sought to examine the role of nuclear translocation on the fibrotic activity of IGFBP-5 and identify IGFBP-5 binding partners relevant for its nuclear compartmentalization.
We generated functional wild type IGFBP-5 and IGFBP-5 with a mutated NLS or a mutated IGF binding site. Abrogation of nuclear translocation in the NLS mutant was confirmed using immunofluorescence and immunoblotting of nuclear and cytoplasmic cellular extracts. Abrogation of IGF binding was confirmed using western ligand blot. The fibrotic activity of wild type and mutant IGFBP-5 was examined in vitro in primary human fibroblasts and ex vivo in human skin. We identified IGFBP-5 binding partners using immunoprecipitation and mass spectrometry. We examined the effect of nucleolin on IGFBP-5 localization and function via sequence-specific silencing in primary human fibroblasts.
Our results show that IGFBP-5-induced ECM production in vitro in primary human fibroblasts is independent of its nuclear translocation. The NLS-mutant also induced fibrosis ex vivo in human skin, thus confirming and extending the in vitro findings. Similar findings were obtained with the IGF-binding mutant. Nucleolin, a nucleolar protein that can serve as a nuclear receptor, was identified as an IGFBP-5 binding partner. Silencing nucleolin reduced IGFBP-5 translocation to the nucleus but did not block the ability of IGFBP-5 to induce ECM production and a fibrotic phenotype.
IGFBP-5 transport to the nucleus requires an intact NLS and nucleolin. However, nuclear translocation is not necessary for IGFBP-5 fibrotic activity; neither is IGF binding. Our data provide further insights into the role of cellular compartmentalization in IGFBP-5-induced fibrosis. |
| doi_str_mv | 10.1371/journal.pone.0130546 |
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We generated functional wild type IGFBP-5 and IGFBP-5 with a mutated NLS or a mutated IGF binding site. Abrogation of nuclear translocation in the NLS mutant was confirmed using immunofluorescence and immunoblotting of nuclear and cytoplasmic cellular extracts. Abrogation of IGF binding was confirmed using western ligand blot. The fibrotic activity of wild type and mutant IGFBP-5 was examined in vitro in primary human fibroblasts and ex vivo in human skin. We identified IGFBP-5 binding partners using immunoprecipitation and mass spectrometry. We examined the effect of nucleolin on IGFBP-5 localization and function via sequence-specific silencing in primary human fibroblasts.
Our results show that IGFBP-5-induced ECM production in vitro in primary human fibroblasts is independent of its nuclear translocation. The NLS-mutant also induced fibrosis ex vivo in human skin, thus confirming and extending the in vitro findings. Similar findings were obtained with the IGF-binding mutant. Nucleolin, a nucleolar protein that can serve as a nuclear receptor, was identified as an IGFBP-5 binding partner. Silencing nucleolin reduced IGFBP-5 translocation to the nucleus but did not block the ability of IGFBP-5 to induce ECM production and a fibrotic phenotype.
IGFBP-5 transport to the nucleus requires an intact NLS and nucleolin. However, nuclear translocation is not necessary for IGFBP-5 fibrotic activity; neither is IGF binding. Our data provide further insights into the role of cellular compartmentalization in IGFBP-5-induced fibrosis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0130546</identifier><identifier>PMID: 26103640</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenoviruses ; Binding sites ; Biochemistry ; Breast cancer ; Cell Nucleus - metabolism ; Extracellular matrix ; Fibroblasts ; Fibrosis ; HIV ; Human immunodeficiency virus ; Humans ; Immunoblotting ; Immunofluorescence ; Immunology ; Immunoprecipitation ; Infections ; Insulin ; Insulin-Like Growth Factor Binding Protein 5 - genetics ; Insulin-Like Growth Factor Binding Protein 5 - physiology ; Insulin-like growth factor-binding protein 5 ; Insulin-like growth factors ; Localization ; Lungs ; Mass spectrometry ; Mass spectroscopy ; Medicine ; Mutants ; Nuclear transport ; Nuclei ; Nucleoli ; Nucleolin ; Phenotypes ; Phosphoproteins - metabolism ; Protein binding ; Protein Transport ; Proteins ; Rheumatology ; RNA-Binding Proteins - metabolism ; Scleroderma ; Scleroderma (Disease) ; Skin ; Smooth muscle ; Somatomedins - metabolism ; Systemic sclerosis ; Translocation</subject><ispartof>PloS one, 2015-06, Vol.10 (6), p.e0130546-e0130546</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Su 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>2015 Su et al 2015 Su et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-f0c411ff3ff8c3e139302e508eea1d561a833a94e63b617ef63f92fa8be6df5a3</citedby><cites>FETCH-LOGICAL-c692t-f0c411ff3ff8c3e139302e508eea1d561a833a94e63b617ef63f92fa8be6df5a3</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/PMC4478026/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4478026/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26103640$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Assassi, Shervin</contributor><creatorcontrib>Su, Yunyun</creatorcontrib><creatorcontrib>Nishimoto, Tetsuya</creatorcontrib><creatorcontrib>Feghali-Bostwick, Carol</creatorcontrib><title>IGFBP-5 Promotes Fibrosis Independently of Its Translocation to the Nucleus and Its Interaction with Nucleolin and IGF</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Insulin-like growth factor binding protein (IGFBP)-5 levels are increased in systemic sclerosis (SSc) skin and lung. We previously reported that IGFBP-5 is a pro-fibrotic factor that induces extracellular matrix (ECM) production and deposition. Since IGFBP-5 contains a nuclear localization signal (NLS) that facilitates its nuclear translocation, we sought to examine the role of nuclear translocation on the fibrotic activity of IGFBP-5 and identify IGFBP-5 binding partners relevant for its nuclear compartmentalization.
We generated functional wild type IGFBP-5 and IGFBP-5 with a mutated NLS or a mutated IGF binding site. Abrogation of nuclear translocation in the NLS mutant was confirmed using immunofluorescence and immunoblotting of nuclear and cytoplasmic cellular extracts. Abrogation of IGF binding was confirmed using western ligand blot. The fibrotic activity of wild type and mutant IGFBP-5 was examined in vitro in primary human fibroblasts and ex vivo in human skin. We identified IGFBP-5 binding partners using immunoprecipitation and mass spectrometry. We examined the effect of nucleolin on IGFBP-5 localization and function via sequence-specific silencing in primary human fibroblasts.
Our results show that IGFBP-5-induced ECM production in vitro in primary human fibroblasts is independent of its nuclear translocation. The NLS-mutant also induced fibrosis ex vivo in human skin, thus confirming and extending the in vitro findings. Similar findings were obtained with the IGF-binding mutant. Nucleolin, a nucleolar protein that can serve as a nuclear receptor, was identified as an IGFBP-5 binding partner. Silencing nucleolin reduced IGFBP-5 translocation to the nucleus but did not block the ability of IGFBP-5 to induce ECM production and a fibrotic phenotype.
IGFBP-5 transport to the nucleus requires an intact NLS and nucleolin. However, nuclear translocation is not necessary for IGFBP-5 fibrotic activity; neither is IGF binding. Our data provide further insights into the role of cellular compartmentalization in IGFBP-5-induced fibrosis.</description><subject>Adenoviruses</subject><subject>Binding sites</subject><subject>Biochemistry</subject><subject>Breast cancer</subject><subject>Cell Nucleus - metabolism</subject><subject>Extracellular matrix</subject><subject>Fibroblasts</subject><subject>Fibrosis</subject><subject>HIV</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Immunofluorescence</subject><subject>Immunology</subject><subject>Immunoprecipitation</subject><subject>Infections</subject><subject>Insulin</subject><subject>Insulin-Like Growth Factor Binding Protein 5 - genetics</subject><subject>Insulin-Like Growth Factor Binding Protein 5 - physiology</subject><subject>Insulin-like growth factor-binding protein 5</subject><subject>Insulin-like growth factors</subject><subject>Localization</subject><subject>Lungs</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Medicine</subject><subject>Mutants</subject><subject>Nuclear transport</subject><subject>Nuclei</subject><subject>Nucleoli</subject><subject>Nucleolin</subject><subject>Phenotypes</subject><subject>Phosphoproteins - metabolism</subject><subject>Protein binding</subject><subject>Protein Transport</subject><subject>Proteins</subject><subject>Rheumatology</subject><subject>RNA-Binding Proteins - metabolism</subject><subject>Scleroderma</subject><subject>Scleroderma (Disease)</subject><subject>Skin</subject><subject>Smooth muscle</subject><subject>Somatomedins - metabolism</subject><subject>Systemic sclerosis</subject><subject>Translocation</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</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>eNqNk1Fv0zAQxyMEYmPwDRBEQkLw0GLHiZu8II2JlkgTm2Dwal2Sc-vJtYvtDPbtcdtsatAekCXbsn_3v_P5LkleUjKlbEY_XNveGdDTjTU4JZSRIuePkmNasWzCM8IeH-yPkmfeXxNSsJLzp8lRxilhPCfHyU29mH-6nBTppbNrG9Cnc9U465VPa9PhBuNkgr5NrUzr4NMrB8Zr20JQ1qTBpmGF6de-1dj7FEy3g2oT0EG7Q36rsNoDViuzRxbz58kTCdrji2E9SX7MP1-dfZmcXyzqs9PzScurLEwkaXNKpWRSli1DyipGMixIiQi0KziFkjGocuSs4XSGkjNZZRLKBnknC2Anyeu97kZbL4aUeUF5RXjBGSORqPdEZ-FabJxag7sVFpTYHVi3FOCCivGLrOkApMwJsDIvedHMGia7GBNryKxgTdT6OHjrmzV2bcycAz0SHd8YtRJLeyPyfFaSjEeBd4OAs7969EGslW9RazBo-13cNCvLWb6N-80_6MOvG6glxAcoI230225FxWlOI5YVVRmp6QNUHB2uVRvrS6p4PjJ4PzKITMA_YQm996L-_u3_2YufY_btAbtC0GHlre63leTHYL4H21ir3qG8TzIlYtsed9kQ2_YQQ3tEs1eHH3RvdNcP7C8gmwpG</recordid><startdate>20150623</startdate><enddate>20150623</enddate><creator>Su, Yunyun</creator><creator>Nishimoto, Tetsuya</creator><creator>Feghali-Bostwick, Carol</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>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150623</creationdate><title>IGFBP-5 Promotes Fibrosis Independently of Its Translocation to the Nucleus and Its Interaction with Nucleolin and IGF</title><author>Su, Yunyun ; Nishimoto, Tetsuya ; Feghali-Bostwick, Carol</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-f0c411ff3ff8c3e139302e508eea1d561a833a94e63b617ef63f92fa8be6df5a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adenoviruses</topic><topic>Binding sites</topic><topic>Biochemistry</topic><topic>Breast cancer</topic><topic>Cell Nucleus - metabolism</topic><topic>Extracellular matrix</topic><topic>Fibroblasts</topic><topic>Fibrosis</topic><topic>HIV</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Immunofluorescence</topic><topic>Immunology</topic><topic>Immunoprecipitation</topic><topic>Infections</topic><topic>Insulin</topic><topic>Insulin-Like Growth Factor Binding Protein 5 - genetics</topic><topic>Insulin-Like Growth Factor Binding Protein 5 - physiology</topic><topic>Insulin-like growth factor-binding protein 5</topic><topic>Insulin-like growth factors</topic><topic>Localization</topic><topic>Lungs</topic><topic>Mass spectrometry</topic><topic>Mass spectroscopy</topic><topic>Medicine</topic><topic>Mutants</topic><topic>Nuclear transport</topic><topic>Nuclei</topic><topic>Nucleoli</topic><topic>Nucleolin</topic><topic>Phenotypes</topic><topic>Phosphoproteins - metabolism</topic><topic>Protein binding</topic><topic>Protein Transport</topic><topic>Proteins</topic><topic>Rheumatology</topic><topic>RNA-Binding Proteins - metabolism</topic><topic>Scleroderma</topic><topic>Scleroderma (Disease)</topic><topic>Skin</topic><topic>Smooth muscle</topic><topic>Somatomedins - metabolism</topic><topic>Systemic sclerosis</topic><topic>Translocation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Su, Yunyun</creatorcontrib><creatorcontrib>Nishimoto, Tetsuya</creatorcontrib><creatorcontrib>Feghali-Bostwick, Carol</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 - 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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>Su, Yunyun</au><au>Nishimoto, Tetsuya</au><au>Feghali-Bostwick, Carol</au><au>Assassi, Shervin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>IGFBP-5 Promotes Fibrosis Independently of Its Translocation to the Nucleus and Its Interaction with Nucleolin and IGF</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-06-23</date><risdate>2015</risdate><volume>10</volume><issue>6</issue><spage>e0130546</spage><epage>e0130546</epage><pages>e0130546-e0130546</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Insulin-like growth factor binding protein (IGFBP)-5 levels are increased in systemic sclerosis (SSc) skin and lung. We previously reported that IGFBP-5 is a pro-fibrotic factor that induces extracellular matrix (ECM) production and deposition. Since IGFBP-5 contains a nuclear localization signal (NLS) that facilitates its nuclear translocation, we sought to examine the role of nuclear translocation on the fibrotic activity of IGFBP-5 and identify IGFBP-5 binding partners relevant for its nuclear compartmentalization.
We generated functional wild type IGFBP-5 and IGFBP-5 with a mutated NLS or a mutated IGF binding site. Abrogation of nuclear translocation in the NLS mutant was confirmed using immunofluorescence and immunoblotting of nuclear and cytoplasmic cellular extracts. Abrogation of IGF binding was confirmed using western ligand blot. The fibrotic activity of wild type and mutant IGFBP-5 was examined in vitro in primary human fibroblasts and ex vivo in human skin. We identified IGFBP-5 binding partners using immunoprecipitation and mass spectrometry. We examined the effect of nucleolin on IGFBP-5 localization and function via sequence-specific silencing in primary human fibroblasts.
Our results show that IGFBP-5-induced ECM production in vitro in primary human fibroblasts is independent of its nuclear translocation. The NLS-mutant also induced fibrosis ex vivo in human skin, thus confirming and extending the in vitro findings. Similar findings were obtained with the IGF-binding mutant. Nucleolin, a nucleolar protein that can serve as a nuclear receptor, was identified as an IGFBP-5 binding partner. Silencing nucleolin reduced IGFBP-5 translocation to the nucleus but did not block the ability of IGFBP-5 to induce ECM production and a fibrotic phenotype.
IGFBP-5 transport to the nucleus requires an intact NLS and nucleolin. However, nuclear translocation is not necessary for IGFBP-5 fibrotic activity; neither is IGF binding. Our data provide further insights into the role of cellular compartmentalization in IGFBP-5-induced fibrosis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26103640</pmid><doi>10.1371/journal.pone.0130546</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Adenoviruses Binding sites Biochemistry Breast cancer Cell Nucleus - metabolism Extracellular matrix Fibroblasts Fibrosis HIV Human immunodeficiency virus Humans Immunoblotting Immunofluorescence Immunology Immunoprecipitation Infections Insulin Insulin-Like Growth Factor Binding Protein 5 - genetics Insulin-Like Growth Factor Binding Protein 5 - physiology Insulin-like growth factor-binding protein 5 Insulin-like growth factors Localization Lungs Mass spectrometry Mass spectroscopy Medicine Mutants Nuclear transport Nuclei Nucleoli Nucleolin Phenotypes Phosphoproteins - metabolism Protein binding Protein Transport Proteins Rheumatology RNA-Binding Proteins - metabolism Scleroderma Scleroderma (Disease) Skin Smooth muscle Somatomedins - metabolism Systemic sclerosis Translocation |
| title | IGFBP-5 Promotes Fibrosis Independently of Its Translocation to the Nucleus and Its Interaction with Nucleolin and IGF |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T19%3A26%3A32IST&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=IGFBP-5%20Promotes%20Fibrosis%20Independently%20of%20Its%20Translocation%20to%20the%20Nucleus%20and%20Its%20Interaction%20with%20Nucleolin%20and%20IGF&rft.jtitle=PloS%20one&rft.au=Su,%20Yunyun&rft.date=2015-06-23&rft.volume=10&rft.issue=6&rft.spage=e0130546&rft.epage=e0130546&rft.pages=e0130546-e0130546&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0130546&rft_dat=%3Cgale_plos_%3EA419062598%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=1690656330&rft_id=info:pmid/26103640&rft_galeid=A419062598&rft_doaj_id=oai_doaj_org_article_2bdaaff40a384865b7b3fd3933b0753b&rfr_iscdi=true |