Inductive differentiation of conjunctival goblet cells by γ-secretase inhibitor and construction of recombinant conjunctival epithelium
γ-secretase inhibitor has been shown to promote intestinal goblet cell differentiation. We now demonstrated that the in vitro addition of γ-secretase inhibitor in the culture of human conjunctival epithelial cells significantly promoted the differentiation of conjunctival goblet cells with typical d...
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Veröffentlicht in: | Experimental eye research 2014-06, Vol.123, p.37-42 |
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description | γ-secretase inhibitor has been shown to promote intestinal goblet cell differentiation. We now demonstrated that the in vitro addition of γ-secretase inhibitor in the culture of human conjunctival epithelial cells significantly promoted the differentiation of conjunctival goblet cells with typical droplet-like phenotype, positive periodic acid-Schiff and goblet cell-specific Muc5Ac, cytokeratin 7 and Helix pomatia agglutinin lectin staining. Moreover, topical application of γ-secretase inhibitor promoted the differentiation of mouse conjunctival goblet cells in vivo. Furthermore, the expression of Notch target gene HES-1 was down-regulated during the differentiation of conjunctival goblet cells. In addition, we found that the recombinant conjunctival epithelium on amniotic membrane showed less goblet cell density and abnormal location when compared with normal conjunctival epithelium, which were improved by the addition of γ-secretase inhibitor in the final induction.
•γ-Secretase inhibitor promoted the differentiation of conjunctival goblet cells in vitro and in vivo.•γ-Secretase inhibitor repressed the Notch target gene HES-1 expression during conjunctival goblet cell differentiation.•γ-Secretase inhibitor improved the goblet cell density and location of the recombinant conjunctival epithelium. |
doi_str_mv | 10.1016/j.exer.2014.04.001 |
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•γ-Secretase inhibitor promoted the differentiation of conjunctival goblet cells in vitro and in vivo.•γ-Secretase inhibitor repressed the Notch target gene HES-1 expression during conjunctival goblet cell differentiation.•γ-Secretase inhibitor improved the goblet cell density and location of the recombinant conjunctival epithelium.</description><identifier>ISSN: 0014-4835</identifier><identifier>EISSN: 1096-0007</identifier><identifier>DOI: 10.1016/j.exer.2014.04.001</identifier><identifier>PMID: 24746620</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Amnion ; Amyloid Precursor Protein Secretases - antagonists & inhibitors ; Animals ; Basic Helix-Loop-Helix Transcription Factors - metabolism ; Blotting, Western ; Cell Count ; Cell Differentiation - physiology ; Cells, Cultured ; Conjunctiva - cytology ; Conjunctiva - metabolism ; conjuntival goblet cells ; differentiation ; Dipeptides - pharmacology ; Enzyme Inhibitors - pharmacology ; Fluorescent Antibody Technique, Indirect ; Goblet Cells - cytology ; Goblet Cells - metabolism ; HES-1 ; Homeodomain Proteins - metabolism ; Humans ; Keratin-7 - genetics ; Keratin-7 - metabolism ; Lectins - metabolism ; Mice ; Mice, Inbred C57BL ; Mucin 5AC - metabolism ; recombinant conjunctiva epithelium ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - metabolism ; Transcription Factor HES-1 ; γ-secretase inhibitor</subject><ispartof>Experimental eye research, 2014-06, Vol.123, p.37-42</ispartof><rights>2014 Elsevier Ltd</rights><rights>Copyright © 2014 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-5b8523f57ff70b29bb5d21d94ccde959c620cd44d3d5c5404c54a53a0c52a5603</citedby><cites>FETCH-LOGICAL-c356t-5b8523f57ff70b29bb5d21d94ccde959c620cd44d3d5c5404c54a53a0c52a5603</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.exer.2014.04.001$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24746620$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tian, Le</creatorcontrib><creatorcontrib>Qu, Mingli</creatorcontrib><creatorcontrib>Wang, Yao</creatorcontrib><creatorcontrib>Duan, Haoyun</creatorcontrib><creatorcontrib>Di, Guohu</creatorcontrib><creatorcontrib>Xie, Lixin</creatorcontrib><creatorcontrib>Zhou, Qingjun</creatorcontrib><title>Inductive differentiation of conjunctival goblet cells by γ-secretase inhibitor and construction of recombinant conjunctival epithelium</title><title>Experimental eye research</title><addtitle>Exp Eye Res</addtitle><description>γ-secretase inhibitor has been shown to promote intestinal goblet cell differentiation. We now demonstrated that the in vitro addition of γ-secretase inhibitor in the culture of human conjunctival epithelial cells significantly promoted the differentiation of conjunctival goblet cells with typical droplet-like phenotype, positive periodic acid-Schiff and goblet cell-specific Muc5Ac, cytokeratin 7 and Helix pomatia agglutinin lectin staining. Moreover, topical application of γ-secretase inhibitor promoted the differentiation of mouse conjunctival goblet cells in vivo. Furthermore, the expression of Notch target gene HES-1 was down-regulated during the differentiation of conjunctival goblet cells. In addition, we found that the recombinant conjunctival epithelium on amniotic membrane showed less goblet cell density and abnormal location when compared with normal conjunctival epithelium, which were improved by the addition of γ-secretase inhibitor in the final induction.
•γ-Secretase inhibitor promoted the differentiation of conjunctival goblet cells in vitro and in vivo.•γ-Secretase inhibitor repressed the Notch target gene HES-1 expression during conjunctival goblet cell differentiation.•γ-Secretase inhibitor improved the goblet cell density and location of the recombinant conjunctival epithelium.</description><subject>Amnion</subject><subject>Amyloid Precursor Protein Secretases - antagonists & inhibitors</subject><subject>Animals</subject><subject>Basic Helix-Loop-Helix Transcription Factors - metabolism</subject><subject>Blotting, Western</subject><subject>Cell Count</subject><subject>Cell Differentiation - physiology</subject><subject>Cells, Cultured</subject><subject>Conjunctiva - cytology</subject><subject>Conjunctiva - metabolism</subject><subject>conjuntival goblet cells</subject><subject>differentiation</subject><subject>Dipeptides - pharmacology</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Fluorescent Antibody Technique, Indirect</subject><subject>Goblet Cells - cytology</subject><subject>Goblet Cells - metabolism</subject><subject>HES-1</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Humans</subject><subject>Keratin-7 - genetics</subject><subject>Keratin-7 - metabolism</subject><subject>Lectins - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mucin 5AC - metabolism</subject><subject>recombinant conjunctiva epithelium</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - metabolism</subject><subject>Transcription Factor HES-1</subject><subject>γ-secretase inhibitor</subject><issn>0014-4835</issn><issn>1096-0007</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UUtqHDEUFCbBHju5gBdBy2x68qSWeqbBm2DsxGDIJlkLfV7bGrqliaQ28Q1yn9zDZ4qasQ3ZBB568FRVUFWEnDNYM2Ddp90af2Fac2BiDXWAHZEVg75rAGDzhqzqRTRi28oTcprzrl5bsRHH5ITX1XUcVuT3TXCzLf4BqfPDgAlD8br4GGgcqI1hN4flW4_0LpoRC7U4jpmaR_r0p8loExadkfpw740vMVEd3MLLJS26B52ENk7GBx3Kv5q49-UeRz9P78jbQY8Z3z_vM_Lj-ur75dfm9tuXm8vPt41tZVcaabaSt4PcDMMGDO-NkY4z1wtrHfayt9WVdUK41kkrBYj6aNlqsJJr2UF7Rj4edPcp_pwxFzX5vHjSAeOcFZMt70VNbluh_AC1KeaccFD75CedHhUDtTSgdmppQC0NKKgDrJI-POvPZkL3SnmJvAIuDgCsLh98pWfrMVh0vsZUlIv-f_p_AUrEm_8</recordid><startdate>20140601</startdate><enddate>20140601</enddate><creator>Tian, Le</creator><creator>Qu, Mingli</creator><creator>Wang, Yao</creator><creator>Duan, Haoyun</creator><creator>Di, Guohu</creator><creator>Xie, Lixin</creator><creator>Zhou, Qingjun</creator><general>Elsevier Ltd</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>7X8</scope></search><sort><creationdate>20140601</creationdate><title>Inductive differentiation of conjunctival goblet cells by γ-secretase inhibitor and construction of recombinant conjunctival epithelium</title><author>Tian, Le ; Qu, Mingli ; Wang, Yao ; Duan, Haoyun ; Di, Guohu ; Xie, Lixin ; Zhou, Qingjun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-5b8523f57ff70b29bb5d21d94ccde959c620cd44d3d5c5404c54a53a0c52a5603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Amnion</topic><topic>Amyloid Precursor Protein Secretases - antagonists & inhibitors</topic><topic>Animals</topic><topic>Basic Helix-Loop-Helix Transcription Factors - metabolism</topic><topic>Blotting, Western</topic><topic>Cell Count</topic><topic>Cell Differentiation - physiology</topic><topic>Cells, Cultured</topic><topic>Conjunctiva - cytology</topic><topic>Conjunctiva - metabolism</topic><topic>conjuntival goblet cells</topic><topic>differentiation</topic><topic>Dipeptides - pharmacology</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Fluorescent Antibody Technique, Indirect</topic><topic>Goblet Cells - cytology</topic><topic>Goblet Cells - metabolism</topic><topic>HES-1</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Humans</topic><topic>Keratin-7 - genetics</topic><topic>Keratin-7 - metabolism</topic><topic>Lectins - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mucin 5AC - metabolism</topic><topic>recombinant conjunctiva epithelium</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - metabolism</topic><topic>Transcription Factor HES-1</topic><topic>γ-secretase inhibitor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tian, Le</creatorcontrib><creatorcontrib>Qu, Mingli</creatorcontrib><creatorcontrib>Wang, Yao</creatorcontrib><creatorcontrib>Duan, Haoyun</creatorcontrib><creatorcontrib>Di, Guohu</creatorcontrib><creatorcontrib>Xie, Lixin</creatorcontrib><creatorcontrib>Zhou, Qingjun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental eye research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tian, Le</au><au>Qu, Mingli</au><au>Wang, Yao</au><au>Duan, Haoyun</au><au>Di, Guohu</au><au>Xie, Lixin</au><au>Zhou, Qingjun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inductive differentiation of conjunctival goblet cells by γ-secretase inhibitor and construction of recombinant conjunctival epithelium</atitle><jtitle>Experimental eye research</jtitle><addtitle>Exp Eye Res</addtitle><date>2014-06-01</date><risdate>2014</risdate><volume>123</volume><spage>37</spage><epage>42</epage><pages>37-42</pages><issn>0014-4835</issn><eissn>1096-0007</eissn><abstract>γ-secretase inhibitor has been shown to promote intestinal goblet cell differentiation. We now demonstrated that the in vitro addition of γ-secretase inhibitor in the culture of human conjunctival epithelial cells significantly promoted the differentiation of conjunctival goblet cells with typical droplet-like phenotype, positive periodic acid-Schiff and goblet cell-specific Muc5Ac, cytokeratin 7 and Helix pomatia agglutinin lectin staining. Moreover, topical application of γ-secretase inhibitor promoted the differentiation of mouse conjunctival goblet cells in vivo. Furthermore, the expression of Notch target gene HES-1 was down-regulated during the differentiation of conjunctival goblet cells. In addition, we found that the recombinant conjunctival epithelium on amniotic membrane showed less goblet cell density and abnormal location when compared with normal conjunctival epithelium, which were improved by the addition of γ-secretase inhibitor in the final induction.
•γ-Secretase inhibitor promoted the differentiation of conjunctival goblet cells in vitro and in vivo.•γ-Secretase inhibitor repressed the Notch target gene HES-1 expression during conjunctival goblet cell differentiation.•γ-Secretase inhibitor improved the goblet cell density and location of the recombinant conjunctival epithelium.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>24746620</pmid><doi>10.1016/j.exer.2014.04.001</doi><tpages>6</tpages></addata></record> |
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subjects | Amnion Amyloid Precursor Protein Secretases - antagonists & inhibitors Animals Basic Helix-Loop-Helix Transcription Factors - metabolism Blotting, Western Cell Count Cell Differentiation - physiology Cells, Cultured Conjunctiva - cytology Conjunctiva - metabolism conjuntival goblet cells differentiation Dipeptides - pharmacology Enzyme Inhibitors - pharmacology Fluorescent Antibody Technique, Indirect Goblet Cells - cytology Goblet Cells - metabolism HES-1 Homeodomain Proteins - metabolism Humans Keratin-7 - genetics Keratin-7 - metabolism Lectins - metabolism Mice Mice, Inbred C57BL Mucin 5AC - metabolism recombinant conjunctiva epithelium Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - metabolism Transcription Factor HES-1 γ-secretase inhibitor |
title | Inductive differentiation of conjunctival goblet cells by γ-secretase inhibitor and construction of recombinant conjunctival epithelium |
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