Journal article

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

Abstract

The sequelae of diabetes include microvascular complications such as diabetic kidney disease (DKD), which involves glucose-mediated renal injury 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; conventional renoprotective agents did not therapeutically target this elevation. C5a and its receptor (C5aR1) were upregulated early in the disease process and prior to manifest kidney injury in several div..

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Grants

Awarded by JDRF Innovative grant


Awarded by Australian National Health and Medical Research Council Career Development Fellowship


Funding Acknowledgements

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.