Protection of the Transplant Kidney from Preservation Injury by Inhibition of Matrix Metalloproteinases
Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, play an important role in ischemic injury to the heart, yet it is not known if these MMPs are involved in the injury that occurs to the transplant kidney. We therefore studied the pharmacologic protection of transplant kidneys during ma...
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| creator | Moser, Michael A J Arcand, Steve Lin, Han-Bin Wojnarowicz, Chris Sawicka, Jolanta Banerjee, Tamalina Luo, Yigang Beck, Gavin R Luke, Patrick P Sawicki, Grzegorz |
| description | Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, play an important role in ischemic injury to the heart, yet it is not known if these MMPs are involved in the injury that occurs to the transplant kidney. We therefore studied the pharmacologic protection of transplant kidneys during machine cold perfusion.
Human kidney perfusates were analyzed for the presence of injury markers such as cytochrome c oxidase, lactate dehydrogenase, and neutrophil-gelatinase associated lipocalin (NGAL), and MMP-2 and MMP-9 were measured. The effects of MMP inhibitors MMP-2 siRNA and doxycycline were studied in an animal model of donation after circulatory determination of death (DCDD).
Markers of injury were present in all analyzed perfusates, with higher levels seen in perfusates from human kidneys donated after controlled DCDD compared to brain death and in perfusate from kidneys with delayed graft function. When rat kidneys were perfused at 4°C for 22 hours with the addition of MMP inhibitors, this resulted in markedly reduced levels of MMP-2, MMP-9 and analyzed injury markers.
Based on our study, MMPs are involved in preservation injury and the supplementation of preservation solution with MMP inhibitors is a potential novel strategy in protecting the transplant kidney from preservation injury. |
| doi_str_mv | 10.1371/journal.pone.0157508 |
| format | Article |
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Human kidney perfusates were analyzed for the presence of injury markers such as cytochrome c oxidase, lactate dehydrogenase, and neutrophil-gelatinase associated lipocalin (NGAL), and MMP-2 and MMP-9 were measured. The effects of MMP inhibitors MMP-2 siRNA and doxycycline were studied in an animal model of donation after circulatory determination of death (DCDD).
Markers of injury were present in all analyzed perfusates, with higher levels seen in perfusates from human kidneys donated after controlled DCDD compared to brain death and in perfusate from kidneys with delayed graft function. When rat kidneys were perfused at 4°C for 22 hours with the addition of MMP inhibitors, this resulted in markedly reduced levels of MMP-2, MMP-9 and analyzed injury markers.
Based on our study, MMPs are involved in preservation injury and the supplementation of preservation solution with MMP inhibitors is a potential novel strategy in protecting the transplant kidney from preservation injury.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0157508</identifier><identifier>PMID: 27327879</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Analysis ; Animal models ; Animals ; Biology and Life Sciences ; Biomarkers ; Biomarkers - metabolism ; Brain ; Cytochrome ; Cytochrome oxidase ; Cytochrome-c oxidase ; Delayed Graft Function - enzymology ; Delayed Graft Function - pathology ; Donations ; Doxycycline ; Doxycycline - pharmacology ; Electron Transport Complex IV - metabolism ; Female ; Gelatinase ; Gelatinase A ; Gelatinase B ; Health aspects ; Heart ; Humans ; Inhibitors ; Injury analysis ; Injury prevention ; Ischemia ; Kidney - drug effects ; Kidney - injuries ; Kidney - pathology ; Kidney - ultrastructure ; Kidney Transplantation ; Kidneys ; L-Lactate dehydrogenase ; L-Lactate Dehydrogenase - metabolism ; Lactate dehydrogenase ; Lactic acid ; Lipocalin ; Lipocalin-2 - metabolism ; Male ; Markers ; Matrix Metalloproteinase 2 - metabolism ; Matrix Metalloproteinase 9 - metabolism ; Matrix Metalloproteinase Inhibitors - pharmacology ; Matrix metalloproteinases ; Matrix Metalloproteinases - metabolism ; Medicine and Health Sciences ; Middle Aged ; Mitochondria - drug effects ; Mitochondria - metabolism ; Models, Animal ; Organ Preservation ; Perfusion ; Pharmacology ; Physiological aspects ; Physiology ; Preservation ; Proteins ; Rats ; Research and Analysis Methods ; Rodents ; siRNA ; Supplements ; Surgery ; Transplants & implants</subject><ispartof>PloS one, 2016-06, Vol.11 (6), p.e0157508-e0157508</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Moser 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>2016 Moser et al 2016 Moser et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c725t-9fc9c0a31b201b26f4491015fe46e9189294f6e24df2592143e98512ea79d6923</citedby><cites>FETCH-LOGICAL-c725t-9fc9c0a31b201b26f4491015fe46e9189294f6e24df2592143e98512ea79d6923</cites><orcidid>0000-0003-0735-199X</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/PMC4915675/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915675/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27327879$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moser, Michael A J</creatorcontrib><creatorcontrib>Arcand, Steve</creatorcontrib><creatorcontrib>Lin, Han-Bin</creatorcontrib><creatorcontrib>Wojnarowicz, Chris</creatorcontrib><creatorcontrib>Sawicka, Jolanta</creatorcontrib><creatorcontrib>Banerjee, Tamalina</creatorcontrib><creatorcontrib>Luo, Yigang</creatorcontrib><creatorcontrib>Beck, Gavin R</creatorcontrib><creatorcontrib>Luke, Patrick P</creatorcontrib><creatorcontrib>Sawicki, Grzegorz</creatorcontrib><title>Protection of the Transplant Kidney from Preservation Injury by Inhibition of Matrix Metalloproteinases</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, play an important role in ischemic injury to the heart, yet it is not known if these MMPs are involved in the injury that occurs to the transplant kidney. We therefore studied the pharmacologic protection of transplant kidneys during machine cold perfusion.
Human kidney perfusates were analyzed for the presence of injury markers such as cytochrome c oxidase, lactate dehydrogenase, and neutrophil-gelatinase associated lipocalin (NGAL), and MMP-2 and MMP-9 were measured. The effects of MMP inhibitors MMP-2 siRNA and doxycycline were studied in an animal model of donation after circulatory determination of death (DCDD).
Markers of injury were present in all analyzed perfusates, with higher levels seen in perfusates from human kidneys donated after controlled DCDD compared to brain death and in perfusate from kidneys with delayed graft function. When rat kidneys were perfused at 4°C for 22 hours with the addition of MMP inhibitors, this resulted in markedly reduced levels of MMP-2, MMP-9 and analyzed injury markers.
Based on our study, MMPs are involved in preservation injury and the supplementation of preservation solution with MMP inhibitors is a potential novel strategy in protecting the transplant kidney from preservation injury.</description><subject>Adult</subject><subject>Analysis</subject><subject>Animal models</subject><subject>Animals</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Biomarkers - metabolism</subject><subject>Brain</subject><subject>Cytochrome</subject><subject>Cytochrome oxidase</subject><subject>Cytochrome-c oxidase</subject><subject>Delayed Graft Function - enzymology</subject><subject>Delayed Graft Function - pathology</subject><subject>Donations</subject><subject>Doxycycline</subject><subject>Doxycycline - pharmacology</subject><subject>Electron Transport Complex IV - metabolism</subject><subject>Female</subject><subject>Gelatinase</subject><subject>Gelatinase A</subject><subject>Gelatinase B</subject><subject>Health aspects</subject><subject>Heart</subject><subject>Humans</subject><subject>Inhibitors</subject><subject>Injury analysis</subject><subject>Injury prevention</subject><subject>Ischemia</subject><subject>Kidney - drug effects</subject><subject>Kidney - injuries</subject><subject>Kidney - pathology</subject><subject>Kidney - ultrastructure</subject><subject>Kidney Transplantation</subject><subject>Kidneys</subject><subject>L-Lactate dehydrogenase</subject><subject>L-Lactate Dehydrogenase - metabolism</subject><subject>Lactate dehydrogenase</subject><subject>Lactic acid</subject><subject>Lipocalin</subject><subject>Lipocalin-2 - metabolism</subject><subject>Male</subject><subject>Markers</subject><subject>Matrix Metalloproteinase 2 - metabolism</subject><subject>Matrix Metalloproteinase 9 - metabolism</subject><subject>Matrix Metalloproteinase Inhibitors - pharmacology</subject><subject>Matrix metalloproteinases</subject><subject>Matrix Metalloproteinases - metabolism</subject><subject>Medicine and Health Sciences</subject><subject>Middle Aged</subject><subject>Mitochondria - drug effects</subject><subject>Mitochondria - metabolism</subject><subject>Models, Animal</subject><subject>Organ Preservation</subject><subject>Perfusion</subject><subject>Pharmacology</subject><subject>Physiological aspects</subject><subject>Physiology</subject><subject>Preservation</subject><subject>Proteins</subject><subject>Rats</subject><subject>Research and Analysis Methods</subject><subject>Rodents</subject><subject>siRNA</subject><subject>Supplements</subject><subject>Surgery</subject><subject>Transplants & 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pathology</topic><topic>Donations</topic><topic>Doxycycline</topic><topic>Doxycycline - pharmacology</topic><topic>Electron Transport Complex IV - metabolism</topic><topic>Female</topic><topic>Gelatinase</topic><topic>Gelatinase A</topic><topic>Gelatinase B</topic><topic>Health aspects</topic><topic>Heart</topic><topic>Humans</topic><topic>Inhibitors</topic><topic>Injury analysis</topic><topic>Injury prevention</topic><topic>Ischemia</topic><topic>Kidney - drug effects</topic><topic>Kidney - injuries</topic><topic>Kidney - pathology</topic><topic>Kidney - ultrastructure</topic><topic>Kidney Transplantation</topic><topic>Kidneys</topic><topic>L-Lactate dehydrogenase</topic><topic>L-Lactate Dehydrogenase - metabolism</topic><topic>Lactate dehydrogenase</topic><topic>Lactic acid</topic><topic>Lipocalin</topic><topic>Lipocalin-2 - metabolism</topic><topic>Male</topic><topic>Markers</topic><topic>Matrix Metalloproteinase 2 - metabolism</topic><topic>Matrix Metalloproteinase 9 - 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Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moser, Michael A J</au><au>Arcand, Steve</au><au>Lin, Han-Bin</au><au>Wojnarowicz, Chris</au><au>Sawicka, Jolanta</au><au>Banerjee, Tamalina</au><au>Luo, Yigang</au><au>Beck, Gavin R</au><au>Luke, Patrick P</au><au>Sawicki, Grzegorz</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protection of the Transplant Kidney from Preservation Injury by Inhibition of Matrix Metalloproteinases</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2016-06-21</date><risdate>2016</risdate><volume>11</volume><issue>6</issue><spage>e0157508</spage><epage>e0157508</epage><pages>e0157508-e0157508</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, play an important role in ischemic injury to the heart, yet it is not known if these MMPs are involved in the injury that occurs to the transplant kidney. We therefore studied the pharmacologic protection of transplant kidneys during machine cold perfusion.
Human kidney perfusates were analyzed for the presence of injury markers such as cytochrome c oxidase, lactate dehydrogenase, and neutrophil-gelatinase associated lipocalin (NGAL), and MMP-2 and MMP-9 were measured. The effects of MMP inhibitors MMP-2 siRNA and doxycycline were studied in an animal model of donation after circulatory determination of death (DCDD).
Markers of injury were present in all analyzed perfusates, with higher levels seen in perfusates from human kidneys donated after controlled DCDD compared to brain death and in perfusate from kidneys with delayed graft function. When rat kidneys were perfused at 4°C for 22 hours with the addition of MMP inhibitors, this resulted in markedly reduced levels of MMP-2, MMP-9 and analyzed injury markers.
Based on our study, MMPs are involved in preservation injury and the supplementation of preservation solution with MMP inhibitors is a potential novel strategy in protecting the transplant kidney from preservation injury.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27327879</pmid><doi>10.1371/journal.pone.0157508</doi><orcidid>https://orcid.org/0000-0003-0735-199X</orcidid><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1798776926 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adult Analysis Animal models Animals Biology and Life Sciences Biomarkers Biomarkers - metabolism Brain Cytochrome Cytochrome oxidase Cytochrome-c oxidase Delayed Graft Function - enzymology Delayed Graft Function - pathology Donations Doxycycline Doxycycline - pharmacology Electron Transport Complex IV - metabolism Female Gelatinase Gelatinase A Gelatinase B Health aspects Heart Humans Inhibitors Injury analysis Injury prevention Ischemia Kidney - drug effects Kidney - injuries Kidney - pathology Kidney - ultrastructure Kidney Transplantation Kidneys L-Lactate dehydrogenase L-Lactate Dehydrogenase - metabolism Lactate dehydrogenase Lactic acid Lipocalin Lipocalin-2 - metabolism Male Markers Matrix Metalloproteinase 2 - metabolism Matrix Metalloproteinase 9 - metabolism Matrix Metalloproteinase Inhibitors - pharmacology Matrix metalloproteinases Matrix Metalloproteinases - metabolism Medicine and Health Sciences Middle Aged Mitochondria - drug effects Mitochondria - metabolism Models, Animal Organ Preservation Perfusion Pharmacology Physiological aspects Physiology Preservation Proteins Rats Research and Analysis Methods Rodents siRNA Supplements Surgery Transplants & implants |
| title | Protection of the Transplant Kidney from Preservation Injury by Inhibition of Matrix Metalloproteinases |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-11T14%3A10%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=Protection%20of%20the%20Transplant%20Kidney%20from%20Preservation%20Injury%20by%20Inhibition%20of%20Matrix%20Metalloproteinases&rft.jtitle=PloS%20one&rft.au=Moser,%20Michael%20A%20J&rft.date=2016-06-21&rft.volume=11&rft.issue=6&rft.spage=e0157508&rft.epage=e0157508&rft.pages=e0157508-e0157508&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0157508&rft_dat=%3Cgale_plos_%3EA456433938%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=1798776926&rft_id=info:pmid/27327879&rft_galeid=A456433938&rft_doaj_id=oai_doaj_org_article_4ed4548915da4c8aa1e4d87879f9ff57&rfr_iscdi=true |