Complement C5a Induces Renal Injury in Diabetic Kidney Disease by Disrupting Mitochondrial Metabolic Agility
Sih Min Tan, Mark Ziemann, Vicki Thallas-Bonke, Matthew Snelson, Vinod Kumar, Adrienne Laskowski, Tuong-Vi Nguyen, Kevin Huynh, Michele V Clarke, Renata Libianto, Scott T Baker, Alison Skene, David A Power, Richard J MacIsaac, Darren C Henstridge, Rick A Wetsel, Assam El-Osta, Peter J Meikle, Scott G Wilson, Josephine M Forbes Show all
Diabetes | AMER DIABETES ASSOC | Published : 2020
The 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 ..View full abstract
Awarded by JDRF Innovative grant
Awarded by Australian National Health and Medical Research Council Career Development Fellowship
This study was supported by a JDRF Innovative grant (1-SRA-2014-261-Q-R) and a Diabetes Australia Research Program grant. S.M.T. is supported by a JDRF Advanced Postdoctoral Fellowship. E.I.E. was supported by a Viertel Clinical Investigatorship, a Royal Australian College of Physicians-JDRF fellowship, and Sir Edward Weary Dunlop Medical Research Foundation and Diabetes Australia Research Program research grants. T.M.W. was supported by an Australian National Health and Medical Research Council Career Development Fellowship (APP1105420). M.T.C. has received a Career Development Award from JDRF Australia and is the recipient of the Australian Research Council Special Research Initiative in Type 1 Juvenile Diabetes.