Pericytes of Indirect Contact Coculture Decrease Integrity of Inner Blood-Retina Barrier Model In Vitro by Upgrading MMP-2/9 Activity
Inner blood-retina barrier (iBRB) is primarily formed of retinal microvascular endothelial cells (ECs) with tight junctions, which are surrounded and supported by retinal microvascular pericytes (RMPs) and basement membrane. Pericytes are believed to be critically involved in the physiology and path...
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| creator | Yang, Tianye Guo, Liang Fang, Yuan Liang, Mingli Zheng, Yongzheng Pan, Mingdong Meng, Chun Liu, Guanghui |
| description | Inner blood-retina barrier (iBRB) is primarily formed of retinal microvascular endothelial cells (ECs) with tight junctions, which are surrounded and supported by retinal microvascular pericytes (RMPs) and basement membrane. Pericytes are believed to be critically involved in the physiology and pathology of iBRB. However, the underlying mechanism remains to be fully elucidated. We developed a novel in vitro iBRB model which was composed of primary cultures of rat retinal ECs and RMPs based on Transwell system. We tested the involvement of pericytes in the migration and invasion of ECs, examined the expression and activity of matrix metalloproteinase- (MMP-) 2/MMP-9 in the culture, evaluated the TEER and permeability of iBRB, and assessed the expression of ZO-1, occludin, claudin-5, and VE-cadherin of endothelial junctions. We found that RMPs with indirect contact of ECs can increase the expression of MMP-2 and upgrade the activity of MMP-2/9 in the coculture, which subsequently decreased TJ protein abundance of ZO-1 and occludin in ECs, promoted the migration of ECs, and finally reduced the integrity of iBRB. Taken together, our data show that RMP relative location with ECs is involved in the integrity of iBRB via MMP-2/9 and has important implications for treating diabetic retinopathy and other retinal disorders involving iBRB dysfunction. |
| doi_str_mv | 10.1155/2021/7124835 |
| format | Article |
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Pericytes are believed to be critically involved in the physiology and pathology of iBRB. However, the underlying mechanism remains to be fully elucidated. We developed a novel in vitro iBRB model which was composed of primary cultures of rat retinal ECs and RMPs based on Transwell system. We tested the involvement of pericytes in the migration and invasion of ECs, examined the expression and activity of matrix metalloproteinase- (MMP-) 2/MMP-9 in the culture, evaluated the TEER and permeability of iBRB, and assessed the expression of ZO-1, occludin, claudin-5, and VE-cadherin of endothelial junctions. We found that RMPs with indirect contact of ECs can increase the expression of MMP-2 and upgrade the activity of MMP-2/9 in the coculture, which subsequently decreased TJ protein abundance of ZO-1 and occludin in ECs, promoted the migration of ECs, and finally reduced the integrity of iBRB. Taken together, our data show that RMP relative location with ECs is involved in the integrity of iBRB via MMP-2/9 and has important implications for treating diabetic retinopathy and other retinal disorders involving iBRB dysfunction.</description><identifier>ISSN: 0278-0240</identifier><identifier>EISSN: 1875-8630</identifier><identifier>DOI: 10.1155/2021/7124835</identifier><identifier>PMID: 34630739</identifier><language>eng</language><publisher>United States: Hindawi</publisher><subject>Animals ; Blood ; Blood-Retinal Barrier - cytology ; Blood-Retinal Barrier - metabolism ; Cadherins ; Cell culture ; Cell Movement ; Cells, Cultured ; Coculture Techniques ; Diabetes mellitus ; Diabetic retinopathy ; Endothelial cells ; Endothelial Cells - cytology ; Endothelial Cells - metabolism ; Gelatinase A ; Gelatinase B ; Integrity ; Male ; Matrix metalloproteinase ; Matrix Metalloproteinase 2 - metabolism ; Matrix Metalloproteinase 9 - metabolism ; Matrix metalloproteinases ; Metalloproteinase ; Microvasculature ; Models, Biological ; Pericytes ; Pericytes - cytology ; Pericytes - metabolism ; Permeability ; Physiology ; Pore size ; Primary Cell Culture ; Rats ; Retina ; Retina - cytology ; Retina - metabolism ; Retinopathy ; Tight junctions ; Tight Junctions - metabolism ; Zonula occludens-1 protein</subject><ispartof>Disease markers, 2021, Vol.2021, p.7124835-10</ispartof><rights>Copyright © 2021 Tianye Yang et al.</rights><rights>Copyright © 2021 Tianye Yang et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2021 Tianye Yang et al. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3635-9c3f720a659161c9ad73a8c423528f13c2b375b26d9311a80637f8d80deb43c93</citedby><cites>FETCH-LOGICAL-c3635-9c3f720a659161c9ad73a8c423528f13c2b375b26d9311a80637f8d80deb43c93</cites><orcidid>0000-0003-2064-4156 ; 0000-0002-9085-168X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494570/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494570/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,886,4025,27925,27926,27927,53793,53795</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34630739$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Su, Ting</contributor><contributor>Ting Su</contributor><creatorcontrib>Yang, Tianye</creatorcontrib><creatorcontrib>Guo, Liang</creatorcontrib><creatorcontrib>Fang, Yuan</creatorcontrib><creatorcontrib>Liang, Mingli</creatorcontrib><creatorcontrib>Zheng, Yongzheng</creatorcontrib><creatorcontrib>Pan, Mingdong</creatorcontrib><creatorcontrib>Meng, Chun</creatorcontrib><creatorcontrib>Liu, Guanghui</creatorcontrib><title>Pericytes of Indirect Contact Coculture Decrease Integrity of Inner Blood-Retina Barrier Model In Vitro by Upgrading MMP-2/9 Activity</title><title>Disease markers</title><addtitle>Dis Markers</addtitle><description>Inner blood-retina barrier (iBRB) is primarily formed of retinal microvascular endothelial cells (ECs) with tight junctions, which are surrounded and supported by retinal microvascular pericytes (RMPs) and basement membrane. Pericytes are believed to be critically involved in the physiology and pathology of iBRB. However, the underlying mechanism remains to be fully elucidated. We developed a novel in vitro iBRB model which was composed of primary cultures of rat retinal ECs and RMPs based on Transwell system. We tested the involvement of pericytes in the migration and invasion of ECs, examined the expression and activity of matrix metalloproteinase- (MMP-) 2/MMP-9 in the culture, evaluated the TEER and permeability of iBRB, and assessed the expression of ZO-1, occludin, claudin-5, and VE-cadherin of endothelial junctions. We found that RMPs with indirect contact of ECs can increase the expression of MMP-2 and upgrade the activity of MMP-2/9 in the coculture, which subsequently decreased TJ protein abundance of ZO-1 and occludin in ECs, promoted the migration of ECs, and finally reduced the integrity of iBRB. Taken together, our data show that RMP relative location with ECs is involved in the integrity of iBRB via MMP-2/9 and has important implications for treating diabetic retinopathy and other retinal disorders involving iBRB dysfunction.</description><subject>Animals</subject><subject>Blood</subject><subject>Blood-Retinal Barrier - cytology</subject><subject>Blood-Retinal Barrier - metabolism</subject><subject>Cadherins</subject><subject>Cell culture</subject><subject>Cell Movement</subject><subject>Cells, Cultured</subject><subject>Coculture Techniques</subject><subject>Diabetes mellitus</subject><subject>Diabetic retinopathy</subject><subject>Endothelial cells</subject><subject>Endothelial Cells - cytology</subject><subject>Endothelial Cells - metabolism</subject><subject>Gelatinase A</subject><subject>Gelatinase B</subject><subject>Integrity</subject><subject>Male</subject><subject>Matrix metalloproteinase</subject><subject>Matrix Metalloproteinase 2 - metabolism</subject><subject>Matrix Metalloproteinase 9 - metabolism</subject><subject>Matrix metalloproteinases</subject><subject>Metalloproteinase</subject><subject>Microvasculature</subject><subject>Models, Biological</subject><subject>Pericytes</subject><subject>Pericytes - cytology</subject><subject>Pericytes - metabolism</subject><subject>Permeability</subject><subject>Physiology</subject><subject>Pore size</subject><subject>Primary Cell Culture</subject><subject>Rats</subject><subject>Retina</subject><subject>Retina - cytology</subject><subject>Retina - metabolism</subject><subject>Retinopathy</subject><subject>Tight junctions</subject><subject>Tight Junctions - metabolism</subject><subject>Zonula occludens-1 protein</subject><issn>0278-0240</issn><issn>1875-8630</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>EIF</sourceid><recordid>eNp90U1vFCEYB3BiNHat3jwbEi8mOi4vwwxcmrTrW5NubIz1Shh4ZkszCyswNfsB_N7OdtdGPXgigR9_ePJH6DklbykVYs4Io_OWslpy8QDNqGxFJRtOHqIZYa2sCKvJEXqS8w0hlKlaPUZHvJ5Ay9UM_byE5O22QMaxx-fB-QS24EUMxdytdhzKmAC_A5vAZJhMgVXyZbu_ECDhsyFGV32B4oPBZyYlP20uo4NhAvibLynibouvNqtknA8rvFxeVmyu8Kkt_naKeooe9WbI8OywHqOrD--_Lj5VF58_ni9OLyrLGy4qZXnfMmIaoWhDrTKu5UbamnHBZE-5ZR1vRccapzilRpKGt710kjjoam4VP0Yn-9zN2K3BWQglmUFvkl-btNXReP33SfDXehVvtaxVLVoyBbw6BKT4fYRc9NpnC8NgAsQxayYkUTWlavfWy3_oTRxTmMa7U0KKRu7Um72yKeacoL__DCV616_e9asP_U78xZ8D3OPfhU7g9R5c--DMD___uF82OKxu</recordid><startdate>2021</startdate><enddate>2021</enddate><creator>Yang, Tianye</creator><creator>Guo, Liang</creator><creator>Fang, Yuan</creator><creator>Liang, Mingli</creator><creator>Zheng, Yongzheng</creator><creator>Pan, Mingdong</creator><creator>Meng, Chun</creator><creator>Liu, Guanghui</creator><general>Hindawi</general><general>Hindawi Limited</general><scope>RHU</scope><scope>RHW</scope><scope>RHX</scope><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>7QL</scope><scope>7QO</scope><scope>7TK</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2064-4156</orcidid><orcidid>https://orcid.org/0000-0002-9085-168X</orcidid></search><sort><creationdate>2021</creationdate><title>Pericytes of Indirect Contact Coculture Decrease Integrity of Inner Blood-Retina Barrier Model In Vitro by Upgrading MMP-2/9 Activity</title><author>Yang, Tianye ; Guo, Liang ; Fang, Yuan ; Liang, Mingli ; Zheng, Yongzheng ; Pan, Mingdong ; Meng, Chun ; Liu, Guanghui</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3635-9c3f720a659161c9ad73a8c423528f13c2b375b26d9311a80637f8d80deb43c93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Blood</topic><topic>Blood-Retinal Barrier - cytology</topic><topic>Blood-Retinal Barrier - metabolism</topic><topic>Cadherins</topic><topic>Cell culture</topic><topic>Cell Movement</topic><topic>Cells, Cultured</topic><topic>Coculture Techniques</topic><topic>Diabetes mellitus</topic><topic>Diabetic retinopathy</topic><topic>Endothelial cells</topic><topic>Endothelial Cells - cytology</topic><topic>Endothelial Cells - metabolism</topic><topic>Gelatinase A</topic><topic>Gelatinase B</topic><topic>Integrity</topic><topic>Male</topic><topic>Matrix metalloproteinase</topic><topic>Matrix Metalloproteinase 2 - metabolism</topic><topic>Matrix Metalloproteinase 9 - metabolism</topic><topic>Matrix metalloproteinases</topic><topic>Metalloproteinase</topic><topic>Microvasculature</topic><topic>Models, Biological</topic><topic>Pericytes</topic><topic>Pericytes - cytology</topic><topic>Pericytes - metabolism</topic><topic>Permeability</topic><topic>Physiology</topic><topic>Pore size</topic><topic>Primary Cell Culture</topic><topic>Rats</topic><topic>Retina</topic><topic>Retina - cytology</topic><topic>Retina - metabolism</topic><topic>Retinopathy</topic><topic>Tight junctions</topic><topic>Tight Junctions - metabolism</topic><topic>Zonula occludens-1 protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Tianye</creatorcontrib><creatorcontrib>Guo, Liang</creatorcontrib><creatorcontrib>Fang, Yuan</creatorcontrib><creatorcontrib>Liang, Mingli</creatorcontrib><creatorcontrib>Zheng, Yongzheng</creatorcontrib><creatorcontrib>Pan, Mingdong</creatorcontrib><creatorcontrib>Meng, Chun</creatorcontrib><creatorcontrib>Liu, Guanghui</creatorcontrib><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Disease markers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Tianye</au><au>Guo, Liang</au><au>Fang, Yuan</au><au>Liang, Mingli</au><au>Zheng, Yongzheng</au><au>Pan, Mingdong</au><au>Meng, Chun</au><au>Liu, Guanghui</au><au>Su, Ting</au><au>Ting Su</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pericytes of Indirect Contact Coculture Decrease Integrity of Inner Blood-Retina Barrier Model In Vitro by Upgrading MMP-2/9 Activity</atitle><jtitle>Disease markers</jtitle><addtitle>Dis Markers</addtitle><date>2021</date><risdate>2021</risdate><volume>2021</volume><spage>7124835</spage><epage>10</epage><pages>7124835-10</pages><issn>0278-0240</issn><eissn>1875-8630</eissn><abstract>Inner blood-retina barrier (iBRB) is primarily formed of retinal microvascular endothelial cells (ECs) with tight junctions, which are surrounded and supported by retinal microvascular pericytes (RMPs) and basement membrane. Pericytes are believed to be critically involved in the physiology and pathology of iBRB. However, the underlying mechanism remains to be fully elucidated. We developed a novel in vitro iBRB model which was composed of primary cultures of rat retinal ECs and RMPs based on Transwell system. We tested the involvement of pericytes in the migration and invasion of ECs, examined the expression and activity of matrix metalloproteinase- (MMP-) 2/MMP-9 in the culture, evaluated the TEER and permeability of iBRB, and assessed the expression of ZO-1, occludin, claudin-5, and VE-cadherin of endothelial junctions. We found that RMPs with indirect contact of ECs can increase the expression of MMP-2 and upgrade the activity of MMP-2/9 in the coculture, which subsequently decreased TJ protein abundance of ZO-1 and occludin in ECs, promoted the migration of ECs, and finally reduced the integrity of iBRB. Taken together, our data show that RMP relative location with ECs is involved in the integrity of iBRB via MMP-2/9 and has important implications for treating diabetic retinopathy and other retinal disorders involving iBRB dysfunction.</abstract><cop>United States</cop><pub>Hindawi</pub><pmid>34630739</pmid><doi>10.1155/2021/7124835</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-2064-4156</orcidid><orcidid>https://orcid.org/0000-0002-9085-168X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Blood Blood-Retinal Barrier - cytology Blood-Retinal Barrier - metabolism Cadherins Cell culture Cell Movement Cells, Cultured Coculture Techniques Diabetes mellitus Diabetic retinopathy Endothelial cells Endothelial Cells - cytology Endothelial Cells - metabolism Gelatinase A Gelatinase B Integrity Male Matrix metalloproteinase Matrix Metalloproteinase 2 - metabolism Matrix Metalloproteinase 9 - metabolism Matrix metalloproteinases Metalloproteinase Microvasculature Models, Biological Pericytes Pericytes - cytology Pericytes - metabolism Permeability Physiology Pore size Primary Cell Culture Rats Retina Retina - cytology Retina - metabolism Retinopathy Tight junctions Tight Junctions - metabolism Zonula occludens-1 protein |
| title | Pericytes of Indirect Contact Coculture Decrease Integrity of Inner Blood-Retina Barrier Model In Vitro by Upgrading MMP-2/9 Activity |
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