Please use this identifier to cite or link to this item:
Full metadata record
DC FieldValueLanguage
dc.contributor.authorTan, Sih Min-
dc.contributor.authorZiemann, Mark-
dc.contributor.authorThallas-Bonke, Vicki-
dc.contributor.authorSnelson, Matthew-
dc.contributor.authorKumar, Vinod-
dc.contributor.authorLaskowski, Adrienne-
dc.contributor.authorNguyen, Tuong-Vi-
dc.contributor.authorHuynh, Kevin-
dc.contributor.authorClarke, Michele V-
dc.contributor.authorLibianto, Renata-
dc.contributor.authorBaker, Scott T-
dc.contributor.authorSkene, Alison-
dc.contributor.authorPower, David A-
dc.contributor.authorMacIsaac, Richard J-
dc.contributor.authorHenstridge, Darren C-
dc.contributor.authorWetsel, Rick A-
dc.contributor.authorEl-Osta, Assam-
dc.contributor.authorMeikle, Peter J-
dc.contributor.authorWilson, Scott G-
dc.contributor.authorForbes, Josephine M-
dc.contributor.authorCooper, Mark E-
dc.contributor.authorEkinci, Elif I-
dc.contributor.authorWoodruff, Trent M-
dc.contributor.authorCoughlan, Melinda T-
dc.identifier.citationDiabetes 2019; 69(1): 83-89en_US
dc.description.abstractThe sequelae of diabetes mellitus include microvascular complications such as diabetic kidney disease (DKD), which involves glucose-mediated renal injury that is associated with a disruption in mitochondrial metabolic agility, inflammation and fibrosis. We explored the role of the innate immune complement component C5a, a potent mediator of inflammation, in the pathogenesis of DKD in clinical and experimental diabetes. Marked systemic elevation in C5a activity was demonstrated in patients with diabetes which was not therapeutically targeted by conventional renoprotective agents. C5a and its receptor (C5aR1) were upregulated early in the disease process and prior to manifest kidney injury in several diverse rodent models of diabetes. Genetic deletion of C5aR1 in mice conferred protection against diabetes-induced renal injury. Transcriptomic profiling of kidney revealed diabetes-induced downregulation of pathways involved in mitochondrial fatty acid metabolism. Interrogation of the lipidomics signature revealed abnormal cardiolipin remodelling in the diabetic kidney, a cardinal sign of disrupted mitochondrial architecture and bioenergetics. In vivo delivery of an orally active inhibitor of C5aR1 (PMX53) reversed the phenotypic changes and normalized the renal mitochondrial fatty acid profile, cardiolipin remodelling and citric acid cycle intermediates. In vitro exposure of human renal proximal tubular epithelial cells to C5a led to altered mitochondrial respiratory function and reactive oxygen species generation. These studies provide evidence for a pivotal role of the C5a/C5aR1 axis in propagating renal injury in the development of DKD via disruption of mitochondrial agility, establishing a new immunometabolic signalling pathway in DKD.en_US
dc.titleComplement C5a Induces Renal Injury in Diabetic Kidney Disease Via Disruption in Mitochondrial Metabolic Agility.en_US
dc.typeJournal Articleen_US
dc.identifier.affiliationResearch Center for Immunology and Autoimmune Diseases, Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas-Houston, Houston, TX, USAen_US
dc.identifier.affiliationGlycation and Diabetes Group, Mater Research Institute-The University of Queensland, Translational Research Institute, Woolloongabba, Queensland, Australiaen_US
dc.identifier.affiliationAnatomical Pathologyen_US
dc.identifier.affiliationDepartment of Diabetes, Central Clinical School, Alfred Medical Research and Education Precinct, Monash University, Melbourne, Victoria, Australiaen_US
dc.identifier.affiliationDeakin University, School of Life and Environmental Sciences, Geelong, Victoria, Australiaen_US
dc.identifier.affiliationDepartment of Medicine, University of Melbourne, Melbourne, Victoria, Australiaen_US
dc.identifier.affiliationDepartment of Endocrinology & Diabetes, St Vincent's Hospital, Melbourne, Victoria, Australiaen_US
dc.identifier.affiliationBaker Heart & Diabetes Institute, Melbourne, Australiaen_US
dc.identifier.affiliationDepartment of Renal Medicine, Alfred Health, Melbourne, Victoria, Australiaen_US
dc.identifier.affiliationSchool of Biomedical Sciences, University of Queensland, Brisbane, Queensland, Australiaen_US
dc.identifier.affiliationInstitute for Breathing and Sleepen_US
dc.type.austinJournal Article-, Scott T
item.openairetypeJournal Article-
item.fulltextNo Fulltext-
item.languageiso639-1en- (University of Melbourne)- for Breathing and Sleep-
Appears in Collections:Journal articles
Show simple item record

Page view(s)

checked on Apr 17, 2024

Google ScholarTM


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.