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Development of a Functional Glomerulus at the Organ Level on a Chip to Mimic Hypertensive Nephropathy
Glomerular hypertension is an important factor exacerbating glomerular diseases to end-stage renal diseases because, ultimately, it results in glomerular sclerosis (especially in hypertensive and diabetic nephropathy). The precise mechanism of glomerular sclerosis caused by glomerular hypertension i...
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Published in: | Scientific reports 2016-08, Vol.6 (1), p.31771, Article 31771 |
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description | Glomerular hypertension is an important factor exacerbating glomerular diseases to end-stage renal diseases because, ultimately, it results in glomerular sclerosis (especially in hypertensive and diabetic nephropathy). The precise mechanism of glomerular sclerosis caused by glomerular hypertension is unclear, due partly to the absence of suitable in vitro or in vivo models capable of mimicking and regulating the complex mechanical forces and/or organ-level disease processes. We developed a "glomerulus-on-a-chip" (GC) microfluidic device. This device reconstitutes the glomerulus with organ-level glomerular functions to create a disease model-on-a chip that mimics hypertensive nephropathy in humans. It comprises two channels lined by closely opposed layers of glomerular endothelial cells and podocytes that experience fluid flow of physiological conditions to mimic the glomerular microenvironment in vivo. Our results revealed that glomerular mechanical forces have a crucial role in cellular cytoskeletal rearrangement as well as the damage to cells and their junctions that leads to increased glomerular leakage observed in hypertensive nephropathy. Results also showed that the GC could readily and flexibly meet the demands of a renal-disease model. The GC could provide drug screening and toxicology testing, and create potential new personalized and accurate therapeutic platforms for glomerular disease. |
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The precise mechanism of glomerular sclerosis caused by glomerular hypertension is unclear, due partly to the absence of suitable in vitro or in vivo models capable of mimicking and regulating the complex mechanical forces and/or organ-level disease processes. We developed a "glomerulus-on-a-chip" (GC) microfluidic device. This device reconstitutes the glomerulus with organ-level glomerular functions to create a disease model-on-a chip that mimics hypertensive nephropathy in humans. It comprises two channels lined by closely opposed layers of glomerular endothelial cells and podocytes that experience fluid flow of physiological conditions to mimic the glomerular microenvironment in vivo. Our results revealed that glomerular mechanical forces have a crucial role in cellular cytoskeletal rearrangement as well as the damage to cells and their junctions that leads to increased glomerular leakage observed in hypertensive nephropathy. Results also showed that the GC could readily and flexibly meet the demands of a renal-disease model. The GC could provide drug screening and toxicology testing, and create potential new personalized and accurate therapeutic platforms for glomerular disease.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep31771</identifier><identifier>PMID: 27558173</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>Cytoskeleton ; Diabetes mellitus ; Disease ; Drug screening ; End-stage renal disease ; Endothelial cells ; Fluid flow ; Glomerulus ; Hypertension ; Kidney diseases ; Leakage ; Microfluidics ; Mimicry ; Nephropathy ; Sclerosis</subject><ispartof>Scientific reports, 2016-08, Vol.6 (1), p.31771, Article 31771</ispartof><rights>Copyright Nature Publishing Group Aug 2016</rights><rights>Copyright © 2016, Macmillan Publishers Limited 2016 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c509t-a91738ab51ad6313cdafe5d0b26167f183c4d664e5fef73d8b2d63d37b1753733</citedby><cites>FETCH-LOGICAL-c509t-a91738ab51ad6313cdafe5d0b26167f183c4d664e5fef73d8b2d63d37b1753733</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1898644196/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1898644196?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,315,733,786,790,891,25783,27957,27958,37047,44625,53827,53829,75483</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27558173$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Mengying</creatorcontrib><creatorcontrib>Zhang, Xulang</creatorcontrib><creatorcontrib>Wen, Xinyu</creatorcontrib><creatorcontrib>Wu, Taihua</creatorcontrib><creatorcontrib>Wang, Weidong</creatorcontrib><creatorcontrib>Yang, Mingzhou</creatorcontrib><creatorcontrib>Wang, Jing</creatorcontrib><creatorcontrib>Fang, Ming</creatorcontrib><creatorcontrib>Lin, Bingcheng</creatorcontrib><creatorcontrib>Lin, Hongli</creatorcontrib><title>Development of a Functional Glomerulus at the Organ Level on a Chip to Mimic Hypertensive Nephropathy</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><description>Glomerular hypertension is an important factor exacerbating glomerular diseases to end-stage renal diseases because, ultimately, it results in glomerular sclerosis (especially in hypertensive and diabetic nephropathy). The precise mechanism of glomerular sclerosis caused by glomerular hypertension is unclear, due partly to the absence of suitable in vitro or in vivo models capable of mimicking and regulating the complex mechanical forces and/or organ-level disease processes. We developed a "glomerulus-on-a-chip" (GC) microfluidic device. This device reconstitutes the glomerulus with organ-level glomerular functions to create a disease model-on-a chip that mimics hypertensive nephropathy in humans. It comprises two channels lined by closely opposed layers of glomerular endothelial cells and podocytes that experience fluid flow of physiological conditions to mimic the glomerular microenvironment in vivo. Our results revealed that glomerular mechanical forces have a crucial role in cellular cytoskeletal rearrangement as well as the damage to cells and their junctions that leads to increased glomerular leakage observed in hypertensive nephropathy. Results also showed that the GC could readily and flexibly meet the demands of a renal-disease model. The GC could provide drug screening and toxicology testing, and create potential new personalized and accurate therapeutic platforms for glomerular disease.</description><subject>Cytoskeleton</subject><subject>Diabetes mellitus</subject><subject>Disease</subject><subject>Drug screening</subject><subject>End-stage renal disease</subject><subject>Endothelial cells</subject><subject>Fluid flow</subject><subject>Glomerulus</subject><subject>Hypertension</subject><subject>Kidney diseases</subject><subject>Leakage</subject><subject>Microfluidics</subject><subject>Mimicry</subject><subject>Nephropathy</subject><subject>Sclerosis</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNpVkcFLwzAUxoMobswd_Ack4MnDtGmapr0IMt0mTHfRc0jb1zWjbWqSDvbfm7E5Zi4vkN_78t73IXRLgkcS0OTJGugo4ZxcoGEYRGwS0jC8PLsP0NjaTeAPC9OIpNdoEHLGEsLpEMErbKHWXQOtw7rEEs_6NndKt7LG81o3YPq6t1g67CrAK7OWLV7ue7BuPT2tVIedxh-qUTle7DowDlqrtoA_oauM7qSrdjfoqpS1hfGxjtD37O1rupgsV_P36ctykrMgdROZ-pkSmTEii5gSmheyBFYEWRiTmJckoXlUxHEErISS0yLJQs8VlGeEM8opHaHng27XZw0UuV_KyFp0RjXS7ISWSvx_aVUl1norojT17bEXuD8KGP3Tg3Vio3vjvbCCJGkSR96_PfVwoHKjrfe_PP1AArEPRZxC8ezd-Ugn8i8C-gtXBoj3</recordid><startdate>20160825</startdate><enddate>20160825</enddate><creator>Zhou, Mengying</creator><creator>Zhang, Xulang</creator><creator>Wen, Xinyu</creator><creator>Wu, Taihua</creator><creator>Wang, Weidong</creator><creator>Yang, Mingzhou</creator><creator>Wang, Jing</creator><creator>Fang, Ming</creator><creator>Lin, Bingcheng</creator><creator>Lin, Hongli</creator><general>Nature Publishing Group</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope></search><sort><creationdate>20160825</creationdate><title>Development of a Functional Glomerulus at the Organ Level on a Chip to Mimic Hypertensive Nephropathy</title><author>Zhou, Mengying ; 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The precise mechanism of glomerular sclerosis caused by glomerular hypertension is unclear, due partly to the absence of suitable in vitro or in vivo models capable of mimicking and regulating the complex mechanical forces and/or organ-level disease processes. We developed a "glomerulus-on-a-chip" (GC) microfluidic device. This device reconstitutes the glomerulus with organ-level glomerular functions to create a disease model-on-a chip that mimics hypertensive nephropathy in humans. It comprises two channels lined by closely opposed layers of glomerular endothelial cells and podocytes that experience fluid flow of physiological conditions to mimic the glomerular microenvironment in vivo. Our results revealed that glomerular mechanical forces have a crucial role in cellular cytoskeletal rearrangement as well as the damage to cells and their junctions that leads to increased glomerular leakage observed in hypertensive nephropathy. Results also showed that the GC could readily and flexibly meet the demands of a renal-disease model. The GC could provide drug screening and toxicology testing, and create potential new personalized and accurate therapeutic platforms for glomerular disease.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>27558173</pmid><doi>10.1038/srep31771</doi><oa>free_for_read</oa></addata></record> |
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subjects | Cytoskeleton Diabetes mellitus Disease Drug screening End-stage renal disease Endothelial cells Fluid flow Glomerulus Hypertension Kidney diseases Leakage Microfluidics Mimicry Nephropathy Sclerosis |
title | Development of a Functional Glomerulus at the Organ Level on a Chip to Mimic Hypertensive Nephropathy |
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