TY - JOUR
T1 - The dysregulation of metabolic pathways and induction of the pentose phosphate pathway in renal ischaemia–reperfusion injury
AU - Scantlebery, Angelique M. L.
AU - Tammaro, Alessandra
AU - Mills, James D.
AU - Rampanelli, Elena
AU - Kors, Lotte
AU - Teske, Gwendoline J.
AU - Butter, Loes M.
AU - Liebisch, Gerhard
AU - Schmitz, Gerd
AU - Florquin, Sandrine
AU - Leemans, Jaklien C.
AU - Roelofs, Joris J. TH
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
KW - energy metabolism
KW - fatty acid beta-oxidation
KW - ischaemia–reperfusion injury
KW - kidney
KW - lipid accumulation
KW - lipid metabolism
KW - pentose phosphate pathway
UR - http://www.scopus.com/inward/record.url?scp=85100063862&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/path.5605
DO - https://doi.org/10.1002/path.5605
M3 - Article
C2 - 33338266
SN - 0022-3417
VL - 253
SP - 404
EP - 414
JO - Journal of pathology
JF - Journal of pathology
IS - 4
ER -