Journal article
Delineating a role for the mitochondrial permeability transition pore in diabetic kidney disease by targeting cyclophilin D
RSJ Lindblom, GC Higgins, TV Nguyen, M Arnstein, DC Henstridge, C Granata, M Snelson, V Thallas-Bonke, ME Cooper, JM Forbes, MT Coughlan
Clinical Science | PORTLAND PRESS LTD | Published : 2020
DOI: 10.1042/CS20190787
Abstract
Mitochondrial stress has been widely observed in diabetic kidney disease (DKD). Cyclophilin D (CypD) is a functional component of the mitochondrial permeability transition pore (mPTP) which allows the exchange of ions and solutes between the mitochondrial matrix to induce mitochondrial swelling and activation of cell death pathways. CypD has been successfully targeted in other disease contexts to improve mitochondrial function and reduced pathology. Two approaches were used to elucidate the role of CypD and the mPTP in DKD. Firstly, mice with a deletion of the gene encoding CypD (Ppif-/-) were rendered diabetic with streptozotocin (STZ) and followed for 24 weeks. Secondly, Alisporivir, a Cyp..
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Awarded by Juvenile Diabetes Research Foundation United States of America
Funding Acknowledgements
This work was completed with support from: the Australian government Research Training Program [Scholarship (to R.S.J.L.)]; the Australian Diabetes Society [Skip Martin Early Career Fellowship (to M.T.C.)], M.T.C. is currently the recipient of a Career Development Award from JDRF Australia, Australian Research Council Special Research Initiative in Type 1 Juvenile Diabetes [grant number 4-CDA-2016-229-M-B]; the postdoctoral fellowship from JDRF [grant number 1-PDF-2017-421-A-N (to G.C.H.)]; and the National Health and Medical Research Council Research Fellows [grant number 1102935 (to J.M.F.) and grant number 1175760 (to M.E.C.)].