The dysregulation of metabolic pathways and induction of the pentose phosphate pathway in renal ischaemia–reperfusion injury
Lipid accumulation is associated with various forms of acute renal injury; however, the causative factors and pathways underpinning this lipid accumulation have not been thoroughly investigated. In this study, we performed lipidomic profiling of renal tissue following ischaemia–reperfusion injury (I...
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| Veröffentlicht in: | The Journal of pathology 2021-04, Vol.253 (4), p.404-414 |
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| creator | Scantlebery, Angelique ML Tammaro, Alessandra Mills, James D Rampanelli, Elena Kors, Lotte Teske, Gwendoline J Butter, Loes M Liebisch, Gerhard Schmitz, Gerd Florquin, Sandrine Leemans, Jaklien C Roelofs, Joris JTH |
| description | Lipid accumulation is associated with various forms of acute renal injury; however, the causative factors and pathways underpinning this lipid accumulation have not been thoroughly investigated. In this study, we performed lipidomic profiling of renal tissue following ischaemia–reperfusion injury (IRI). We identified a significant accumulation of cholesterol and specific phospholipids and sphingolipids in kidneys 24 h after IRI. In light of these findings, we hypothesised that pathways involved in lipid metabolism may also be altered. Through the analysis of published microarray data, generated from sham and ischaemic kidneys, we identified nephron‐specific metabolic pathways affected by IRI and validated these findings in ischaemic renal tissue. In silico analysis revealed the downregulation of several energy and lipid metabolism pathways, including mitochondrial fatty acid beta‐oxidation (FAO), peroxisomal lipid metabolism, fatty acid (FA) metabolism, and glycolysis. The pentose phosphate pathway (PPP), which is fuelled by glycolysis, was the only metabolic pathway that was upregulated 24 h following IRI. In this study, we describe the effect of renal IRI on metabolic pathways and how this contributes to lipid accumulation. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland. |
| doi_str_mv | 10.1002/path.5605 |
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In this study, we performed lipidomic profiling of renal tissue following ischaemia–reperfusion injury (IRI). We identified a significant accumulation of cholesterol and specific phospholipids and sphingolipids in kidneys 24 h after IRI. In light of these findings, we hypothesised that pathways involved in lipid metabolism may also be altered. Through the analysis of published microarray data, generated from sham and ischaemic kidneys, we identified nephron‐specific metabolic pathways affected by IRI and validated these findings in ischaemic renal tissue. In silico analysis revealed the downregulation of several energy and lipid metabolism pathways, including mitochondrial fatty acid beta‐oxidation (FAO), peroxisomal lipid metabolism, fatty acid (FA) metabolism, and glycolysis. The pentose phosphate pathway (PPP), which is fuelled by glycolysis, was the only metabolic pathway that was upregulated 24 h following IRI. In this study, we describe the effect of renal IRI on metabolic pathways and how this contributes to lipid accumulation. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.</description><identifier>ISSN: 0022-3417</identifier><identifier>EISSN: 1096-9896</identifier><identifier>DOI: 10.1002/path.5605</identifier><identifier>PMID: 33338266</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Cholesterol ; Energy metabolism ; fatty acid beta‐oxidation ; Fatty acids ; Glycolysis ; ischaemia–reperfusion injury ; Ischemia ; kidney ; Kidneys ; Life Sciences & Biomedicine ; lipid accumulation ; Lipid metabolism ; Lipids ; Metabolic pathways ; Metabolism ; Mitochondria ; Oncology ; Original Paper ; Original Papers ; Oxidation ; Pathology ; Pentose phosphate pathway ; Phospholipids ; Reperfusion ; Science & Technology ; Sphingolipids</subject><ispartof>The Journal of pathology, 2021-04, Vol.253 (4), p.404-414</ispartof><rights>2020 The Authors. published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.</rights><rights>2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.</rights><rights>2020. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). 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In this study, we performed lipidomic profiling of renal tissue following ischaemia–reperfusion injury (IRI). We identified a significant accumulation of cholesterol and specific phospholipids and sphingolipids in kidneys 24 h after IRI. In light of these findings, we hypothesised that pathways involved in lipid metabolism may also be altered. Through the analysis of published microarray data, generated from sham and ischaemic kidneys, we identified nephron‐specific metabolic pathways affected by IRI and validated these findings in ischaemic renal tissue. In silico analysis revealed the downregulation of several energy and lipid metabolism pathways, including mitochondrial fatty acid beta‐oxidation (FAO), peroxisomal lipid metabolism, fatty acid (FA) metabolism, and glycolysis. The pentose phosphate pathway (PPP), which is fuelled by glycolysis, was the only metabolic pathway that was upregulated 24 h following IRI. In this study, we describe the effect of renal IRI on metabolic pathways and how this contributes to lipid accumulation. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.</description><subject>Cholesterol</subject><subject>Energy metabolism</subject><subject>fatty acid beta‐oxidation</subject><subject>Fatty acids</subject><subject>Glycolysis</subject><subject>ischaemia–reperfusion injury</subject><subject>Ischemia</subject><subject>kidney</subject><subject>Kidneys</subject><subject>Life Sciences & Biomedicine</subject><subject>lipid accumulation</subject><subject>Lipid metabolism</subject><subject>Lipids</subject><subject>Metabolic pathways</subject><subject>Metabolism</subject><subject>Mitochondria</subject><subject>Oncology</subject><subject>Original Paper</subject><subject>Original Papers</subject><subject>Oxidation</subject><subject>Pathology</subject><subject>Pentose phosphate pathway</subject><subject>Phospholipids</subject><subject>Reperfusion</subject><subject>Science & Technology</subject><subject>Sphingolipids</subject><issn>0022-3417</issn><issn>1096-9896</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>HGBXW</sourceid><recordid>eNqNks9u1DAQxi0EokvhwAugSFxAKK2d2I59qVStCkWqBIflbDneSeNV1g52QpUL4h36hjwJTvePAAmJucxhfvPN5xkj9JLgM4Jxcd7roT1jHLNHaEGw5LkUkj9Gi1Qr8pKS6gQ9i3GDMZaSsafopEwhCs4X6PuqhWw9xQC3Y6cH613mm2wLg659Z002S9_pKWbarTPr1qM5MENq7MENPqbc-ti3eoADn9AsgNNdZqNpNWyt_vnjPkAPoRnjrGDdZgzTc_Sk0V2EF_t8ir68v1otr_ObTx8-Li9vcsOwZLmmhJeCUM610ZQyXBOhRWEwVGVT0kY0FadUyBKXhAGTBiTDpSlqwYqkYMpTdLHT7cd6C2uTfAfdqT7YrQ6T8tqqPyvOturWf1OVFFwWMgm82QsE_3WEOKhtehl0nXbgx6gKWhHKKkZn9PVf6MaPIe1ipmQSk5iQRL3dUSb4mNbfHM0QrOarqnmVar5qYl_97v5IHs6YgHc74A5q30RjwRk4YununJREpMEp5tHi_-mlHR6-xdKPbkit5_tW28H0b8vq8-Xq-sH7L83L0LU</recordid><startdate>202104</startdate><enddate>202104</enddate><creator>Scantlebery, Angelique ML</creator><creator>Tammaro, Alessandra</creator><creator>Mills, James D</creator><creator>Rampanelli, Elena</creator><creator>Kors, Lotte</creator><creator>Teske, Gwendoline J</creator><creator>Butter, Loes M</creator><creator>Liebisch, Gerhard</creator><creator>Schmitz, Gerd</creator><creator>Florquin, Sandrine</creator><creator>Leemans, Jaklien C</creator><creator>Roelofs, Joris JTH</creator><general>John Wiley & Sons, Ltd</general><general>Wiley</general><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>WIN</scope><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7742-0092</orcidid><orcidid>https://orcid.org/0000-0001-9303-6042</orcidid><orcidid>https://orcid.org/0000-0002-0104-6751</orcidid><orcidid>https://orcid.org/0000-0003-4886-0811</orcidid><orcidid>https://orcid.org/0000-0003-3128-5259</orcidid></search><sort><creationdate>202104</creationdate><title>The dysregulation of metabolic pathways and induction of the pentose phosphate pathway in renal ischaemia–reperfusion injury</title><author>Scantlebery, Angelique ML ; 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however, the causative factors and pathways underpinning this lipid accumulation have not been thoroughly investigated. In this study, we performed lipidomic profiling of renal tissue following ischaemia–reperfusion injury (IRI). We identified a significant accumulation of cholesterol and specific phospholipids and sphingolipids in kidneys 24 h after IRI. In light of these findings, we hypothesised that pathways involved in lipid metabolism may also be altered. Through the analysis of published microarray data, generated from sham and ischaemic kidneys, we identified nephron‐specific metabolic pathways affected by IRI and validated these findings in ischaemic renal tissue. In silico analysis revealed the downregulation of several energy and lipid metabolism pathways, including mitochondrial fatty acid beta‐oxidation (FAO), peroxisomal lipid metabolism, fatty acid (FA) metabolism, and glycolysis. The pentose phosphate pathway (PPP), which is fuelled by glycolysis, was the only metabolic pathway that was upregulated 24 h following IRI. In this study, we describe the effect of renal IRI on metabolic pathways and how this contributes to lipid accumulation. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>33338266</pmid><doi>10.1002/path.5605</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-7742-0092</orcidid><orcidid>https://orcid.org/0000-0001-9303-6042</orcidid><orcidid>https://orcid.org/0000-0002-0104-6751</orcidid><orcidid>https://orcid.org/0000-0003-4886-0811</orcidid><orcidid>https://orcid.org/0000-0003-3128-5259</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Cholesterol Energy metabolism fatty acid beta‐oxidation Fatty acids Glycolysis ischaemia–reperfusion injury Ischemia kidney Kidneys Life Sciences & Biomedicine lipid accumulation Lipid metabolism Lipids Metabolic pathways Metabolism Mitochondria Oncology Original Paper Original Papers Oxidation Pathology Pentose phosphate pathway Phospholipids Reperfusion Science & Technology Sphingolipids |
| title | The dysregulation of metabolic pathways and induction of the pentose phosphate pathway in renal ischaemia–reperfusion injury |
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