Loss of EP2 receptor subtype in colonic cells compromise epithelial barrier integrity by altering claudin-4
Prostaglandin E2 (PGE2) is a bioactive lipid mediator that exerts its biological function through interaction with four different subtypes of E-Prostanoid receptor namely EP1, EP2, EP3 and EP4. It has been known that EP2 receptor is differentially over-expressed in the epithelia of inflamed human co...
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| description | Prostaglandin E2 (PGE2) is a bioactive lipid mediator that exerts its biological function through interaction with four different subtypes of E-Prostanoid receptor namely EP1, EP2, EP3 and EP4. It has been known that EP2 receptor is differentially over-expressed in the epithelia of inflamed human colonic mucosa. However, the significance of the differential expression in altering epithelial barrier function is not known. In this study, we used Caco-2 cells expressing EP2 receptor, either high (EP2S) or low (EP2A), as a model epithelia and determined the barrier function of these cell monolayers by measuring the trans epithelial resistance (TER). Basal TER of EP2A (but not EP2S) monolayer was significantly lower suggesting a loss of colonic epithelial barrier integrity. In comparison, the TER of wild type Caco-2 was decreased in response to an EP2 receptor specific antagonist (AH-6809) indicating an important role for EP2 receptor in the maintenance of epithelial barrier function. The decrease TER in EP2A monolayer corresponded with a significant loss of the tight junction (TJ) protein claudin-4 without affecting other major TJ proteins. Similarly, EP2 receptor antagonism/siRNA based silencing significantly decreased claudin-4 expression in EP2S cells. Surprisingly, alteration in claudin-4 was not transcriptionally regulated in EP2A cells but rather undergoes increased proteosomal degradation. Moreover, among the TER compromising cytokines examined (IL-8, IL-1β, TNF-α, IFN-γ) only IFN-γ was significantly up regulated in EP2A cells. However, IFN-γ did not significantly decreased claudin-4 expression in Caco-2 cells indicating no role for IFN-γ in degrading claudin-4. We conclude that differential down-regulation of EP2 receptor play a major role in compromising colonic epithelial barrier function by selectively increasing proteosomal degradation of claudin-4. |
| doi_str_mv | 10.1371/journal.pone.0113270 |
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It has been known that EP2 receptor is differentially over-expressed in the epithelia of inflamed human colonic mucosa. However, the significance of the differential expression in altering epithelial barrier function is not known. In this study, we used Caco-2 cells expressing EP2 receptor, either high (EP2S) or low (EP2A), as a model epithelia and determined the barrier function of these cell monolayers by measuring the trans epithelial resistance (TER). Basal TER of EP2A (but not EP2S) monolayer was significantly lower suggesting a loss of colonic epithelial barrier integrity. In comparison, the TER of wild type Caco-2 was decreased in response to an EP2 receptor specific antagonist (AH-6809) indicating an important role for EP2 receptor in the maintenance of epithelial barrier function. The decrease TER in EP2A monolayer corresponded with a significant loss of the tight junction (TJ) protein claudin-4 without affecting other major TJ proteins. Similarly, EP2 receptor antagonism/siRNA based silencing significantly decreased claudin-4 expression in EP2S cells. Surprisingly, alteration in claudin-4 was not transcriptionally regulated in EP2A cells but rather undergoes increased proteosomal degradation. Moreover, among the TER compromising cytokines examined (IL-8, IL-1β, TNF-α, IFN-γ) only IFN-γ was significantly up regulated in EP2A cells. However, IFN-γ did not significantly decreased claudin-4 expression in Caco-2 cells indicating no role for IFN-γ in degrading claudin-4. We conclude that differential down-regulation of EP2 receptor play a major role in compromising colonic epithelial barrier function by selectively increasing proteosomal degradation of claudin-4.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0113270</identifier><identifier>PMID: 25396731</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Alprostadil - analogs & derivatives ; Alprostadil - pharmacology ; Analysis ; Apoptosis ; Caco-2 Cells ; Cell Membrane Permeability - drug effects ; Claudin-4 - metabolism ; Colon ; Cytokines ; Cytokines - metabolism ; Degradation ; Down-regulation ; Down-Regulation - drug effects ; Humans ; Immunology ; Infectious diseases ; Inflammation ; Inflammatory bowel disease ; Integrity ; Interferon ; Interferon-gamma - metabolism ; Interferon-gamma - pharmacology ; Interleukin 8 ; Laboratories ; Medicine and Health Sciences ; Monolayers ; Monomolecular films ; Mucosa ; Permeability ; Prostaglandin E2 ; Proteins ; Receptors, Prostaglandin E, EP2 Subtype - antagonists & inhibitors ; Receptors, Prostaglandin E, EP2 Subtype - genetics ; Receptors, Prostaglandin E, EP2 Subtype - metabolism ; RNA Interference ; RNA, Messenger - metabolism ; RNA, Small Interfering - metabolism ; Rodents ; siRNA ; Tight Junctions - drug effects ; Tight Junctions - metabolism ; Transcription ; Tumor necrosis factor-α ; Xanthones - pharmacology ; γ-Interferon</subject><ispartof>PloS one, 2014-11, Vol.9 (11), p.e113270-e113270</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Lejeune 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 Lejeune et al 2014 Lejeune et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-b44c7f3c09dee38765dc51d37a7edd10a875e8c807813bb9e4c2b389d3c46d2a3</citedby><cites>FETCH-LOGICAL-c758t-b44c7f3c09dee38765dc51d37a7edd10a875e8c807813bb9e4c2b389d3c46d2a3</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/PMC4232557/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232557/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25396731$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Koval, Michael</contributor><creatorcontrib>Lejeune, Manigandan</creatorcontrib><creatorcontrib>Moreau, France</creatorcontrib><creatorcontrib>Chadee, Kris</creatorcontrib><title>Loss of EP2 receptor subtype in colonic cells compromise epithelial barrier integrity by altering claudin-4</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Prostaglandin E2 (PGE2) is a bioactive lipid mediator that exerts its biological function through interaction with four different subtypes of E-Prostanoid receptor namely EP1, EP2, EP3 and EP4. It has been known that EP2 receptor is differentially over-expressed in the epithelia of inflamed human colonic mucosa. However, the significance of the differential expression in altering epithelial barrier function is not known. In this study, we used Caco-2 cells expressing EP2 receptor, either high (EP2S) or low (EP2A), as a model epithelia and determined the barrier function of these cell monolayers by measuring the trans epithelial resistance (TER). Basal TER of EP2A (but not EP2S) monolayer was significantly lower suggesting a loss of colonic epithelial barrier integrity. In comparison, the TER of wild type Caco-2 was decreased in response to an EP2 receptor specific antagonist (AH-6809) indicating an important role for EP2 receptor in the maintenance of epithelial barrier function. The decrease TER in EP2A monolayer corresponded with a significant loss of the tight junction (TJ) protein claudin-4 without affecting other major TJ proteins. Similarly, EP2 receptor antagonism/siRNA based silencing significantly decreased claudin-4 expression in EP2S cells. Surprisingly, alteration in claudin-4 was not transcriptionally regulated in EP2A cells but rather undergoes increased proteosomal degradation. Moreover, among the TER compromising cytokines examined (IL-8, IL-1β, TNF-α, IFN-γ) only IFN-γ was significantly up regulated in EP2A cells. However, IFN-γ did not significantly decreased claudin-4 expression in Caco-2 cells indicating no role for IFN-γ in degrading claudin-4. We conclude that differential down-regulation of EP2 receptor play a major role in compromising colonic epithelial barrier function by selectively increasing proteosomal degradation of claudin-4.</description><subject>Alprostadil - analogs & derivatives</subject><subject>Alprostadil - pharmacology</subject><subject>Analysis</subject><subject>Apoptosis</subject><subject>Caco-2 Cells</subject><subject>Cell Membrane Permeability - drug effects</subject><subject>Claudin-4 - metabolism</subject><subject>Colon</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Degradation</subject><subject>Down-regulation</subject><subject>Down-Regulation - drug effects</subject><subject>Humans</subject><subject>Immunology</subject><subject>Infectious diseases</subject><subject>Inflammation</subject><subject>Inflammatory bowel disease</subject><subject>Integrity</subject><subject>Interferon</subject><subject>Interferon-gamma - metabolism</subject><subject>Interferon-gamma - pharmacology</subject><subject>Interleukin 8</subject><subject>Laboratories</subject><subject>Medicine and Health Sciences</subject><subject>Monolayers</subject><subject>Monomolecular films</subject><subject>Mucosa</subject><subject>Permeability</subject><subject>Prostaglandin E2</subject><subject>Proteins</subject><subject>Receptors, Prostaglandin E, EP2 Subtype - antagonists & inhibitors</subject><subject>Receptors, Prostaglandin E, EP2 Subtype - genetics</subject><subject>Receptors, Prostaglandin E, EP2 Subtype - metabolism</subject><subject>RNA Interference</subject><subject>RNA, Messenger - metabolism</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Rodents</subject><subject>siRNA</subject><subject>Tight Junctions - drug effects</subject><subject>Tight Junctions - metabolism</subject><subject>Transcription</subject><subject>Tumor necrosis factor-α</subject><subject>Xanthones - pharmacology</subject><subject>γ-Interferon</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>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk12L1DAUhoso7rr6D0QLgujFjPlom-RGWJZVBwZW_LoNaXrayZppukkqzr8343SXqeyF5CJfz3mTvDkny55jtMSU4XfXbvS9ssvB9bBEGFPC0IPsFAtKFhVB9OHR-CR7EsI1QiXlVfU4OyElFRWj-DT7uXYh5K7NLz-T3IOGITqfh7GOuwFy0-faWdcbnWuwNqTZdvBuawLkMJi4AWuUzWvlvQGf8AidN3GX17tc2Qje9F2urRob0y-Kp9mjVtkAz6b-LPv-4fLbxafF-urj6uJ8vdCs5HFRF4VmLdVINACUs6psdIkbyhSDpsFIcVYC1xwxjmldCyg0qSkXDdVF1RBFz7KXB93BuiAnn4LEgglBGUEoEasD0Th1LQdvtsrvpFNG_l1wvpPKR6MtyLYoa6iAEYVRQVgrcFNWSqASdM3bmiat99NpY72FRkMfvbIz0flObzayc79kQSgpS5YE3kwC3t2MEKJM_u7tVj24Md27IpwzQVGR0Ff_oPe_bqI6lR5g-talc_VeVJ4XmJdEVGSvtbyHSq2BrdEpqVqT1mcBb2cBiYnwO3ZqDEGuvn75f_bqx5x9fcRuICXOJjg7RuP6MAeLA6h9SloP7Z3JGMl9Tdy6Ifc1IaeaSGEvjj_oLui2COgf8AUHlg</recordid><startdate>20141114</startdate><enddate>20141114</enddate><creator>Lejeune, Manigandan</creator><creator>Moreau, France</creator><creator>Chadee, Kris</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>AEUYN</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>20141114</creationdate><title>Loss of EP2 receptor subtype in colonic cells compromise epithelial barrier integrity by altering claudin-4</title><author>Lejeune, Manigandan ; Moreau, France ; Chadee, Kris</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-b44c7f3c09dee38765dc51d37a7edd10a875e8c807813bb9e4c2b389d3c46d2a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Alprostadil - analogs & derivatives</topic><topic>Alprostadil - pharmacology</topic><topic>Analysis</topic><topic>Apoptosis</topic><topic>Caco-2 Cells</topic><topic>Cell Membrane Permeability - drug effects</topic><topic>Claudin-4 - metabolism</topic><topic>Colon</topic><topic>Cytokines</topic><topic>Cytokines - metabolism</topic><topic>Degradation</topic><topic>Down-regulation</topic><topic>Down-Regulation - drug effects</topic><topic>Humans</topic><topic>Immunology</topic><topic>Infectious diseases</topic><topic>Inflammation</topic><topic>Inflammatory bowel disease</topic><topic>Integrity</topic><topic>Interferon</topic><topic>Interferon-gamma - metabolism</topic><topic>Interferon-gamma - pharmacology</topic><topic>Interleukin 8</topic><topic>Laboratories</topic><topic>Medicine and Health Sciences</topic><topic>Monolayers</topic><topic>Monomolecular films</topic><topic>Mucosa</topic><topic>Permeability</topic><topic>Prostaglandin E2</topic><topic>Proteins</topic><topic>Receptors, Prostaglandin E, EP2 Subtype - antagonists & inhibitors</topic><topic>Receptors, Prostaglandin E, EP2 Subtype - genetics</topic><topic>Receptors, Prostaglandin E, EP2 Subtype - metabolism</topic><topic>RNA Interference</topic><topic>RNA, Messenger - metabolism</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Rodents</topic><topic>siRNA</topic><topic>Tight Junctions - drug effects</topic><topic>Tight Junctions - metabolism</topic><topic>Transcription</topic><topic>Tumor necrosis factor-α</topic><topic>Xanthones - pharmacology</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lejeune, Manigandan</creatorcontrib><creatorcontrib>Moreau, France</creatorcontrib><creatorcontrib>Chadee, Kris</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>Proquest Nursing & Allied Health Source</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 One Sustainability</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>Lejeune, Manigandan</au><au>Moreau, France</au><au>Chadee, Kris</au><au>Koval, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Loss of EP2 receptor subtype in colonic cells compromise epithelial barrier integrity by altering claudin-4</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-11-14</date><risdate>2014</risdate><volume>9</volume><issue>11</issue><spage>e113270</spage><epage>e113270</epage><pages>e113270-e113270</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Prostaglandin E2 (PGE2) is a bioactive lipid mediator that exerts its biological function through interaction with four different subtypes of E-Prostanoid receptor namely EP1, EP2, EP3 and EP4. It has been known that EP2 receptor is differentially over-expressed in the epithelia of inflamed human colonic mucosa. However, the significance of the differential expression in altering epithelial barrier function is not known. In this study, we used Caco-2 cells expressing EP2 receptor, either high (EP2S) or low (EP2A), as a model epithelia and determined the barrier function of these cell monolayers by measuring the trans epithelial resistance (TER). Basal TER of EP2A (but not EP2S) monolayer was significantly lower suggesting a loss of colonic epithelial barrier integrity. In comparison, the TER of wild type Caco-2 was decreased in response to an EP2 receptor specific antagonist (AH-6809) indicating an important role for EP2 receptor in the maintenance of epithelial barrier function. The decrease TER in EP2A monolayer corresponded with a significant loss of the tight junction (TJ) protein claudin-4 without affecting other major TJ proteins. Similarly, EP2 receptor antagonism/siRNA based silencing significantly decreased claudin-4 expression in EP2S cells. Surprisingly, alteration in claudin-4 was not transcriptionally regulated in EP2A cells but rather undergoes increased proteosomal degradation. Moreover, among the TER compromising cytokines examined (IL-8, IL-1β, TNF-α, IFN-γ) only IFN-γ was significantly up regulated in EP2A cells. However, IFN-γ did not significantly decreased claudin-4 expression in Caco-2 cells indicating no role for IFN-γ in degrading claudin-4. We conclude that differential down-regulation of EP2 receptor play a major role in compromising colonic epithelial barrier function by selectively increasing proteosomal degradation of claudin-4.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25396731</pmid><doi>10.1371/journal.pone.0113270</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Alprostadil - analogs & derivatives Alprostadil - pharmacology Analysis Apoptosis Caco-2 Cells Cell Membrane Permeability - drug effects Claudin-4 - metabolism Colon Cytokines Cytokines - metabolism Degradation Down-regulation Down-Regulation - drug effects Humans Immunology Infectious diseases Inflammation Inflammatory bowel disease Integrity Interferon Interferon-gamma - metabolism Interferon-gamma - pharmacology Interleukin 8 Laboratories Medicine and Health Sciences Monolayers Monomolecular films Mucosa Permeability Prostaglandin E2 Proteins Receptors, Prostaglandin E, EP2 Subtype - antagonists & inhibitors Receptors, Prostaglandin E, EP2 Subtype - genetics Receptors, Prostaglandin E, EP2 Subtype - metabolism RNA Interference RNA, Messenger - metabolism RNA, Small Interfering - metabolism Rodents siRNA Tight Junctions - drug effects Tight Junctions - metabolism Transcription Tumor necrosis factor-α Xanthones - pharmacology γ-Interferon |
| title | Loss of EP2 receptor subtype in colonic cells compromise epithelial barrier integrity by altering claudin-4 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-29T21%3A28%3A16IST&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=Loss%20of%20EP2%20receptor%20subtype%20in%20colonic%20cells%20compromise%20epithelial%20barrier%20integrity%20by%20altering%20claudin-4&rft.jtitle=PloS%20one&rft.au=Lejeune,%20Manigandan&rft.date=2014-11-14&rft.volume=9&rft.issue=11&rft.spage=e113270&rft.epage=e113270&rft.pages=e113270-e113270&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0113270&rft_dat=%3Cgale_plos_%3EA418529624%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=1979937200&rft_id=info:pmid/25396731&rft_galeid=A418529624&rft_doaj_id=oai_doaj_org_article_f45be6e72a10427f91d56a905ecb8fb3&rfr_iscdi=true |