%0 Journal Article
%A Micakovic, Tamara
%A Papagiannarou, Stamatia
%A Clark, Euan
%A Kuzay, Yalcin
%A Abramovic, Katarina
%A Peters, Jörg
%A Sticht, Carsten
%A Volk, Nadine
%A Fleming, Thomas
%A Nawroth, Peter
%A Hammes, Hans-Peter
%A Alenina, Natalia
%A Gröne, Hermann-Josef
%A Hoffmann, Sigrid Christa
%T The angiotensin II type 2 receptors protect renal tubule mitochondria in early stages of diabetes mellitus.
%J Kidney international
%V 94
%N 5
%@ 0085-2538
%C Basingstoke
%I Nature Publishing Group
%M DKFZ-2018-01453
%P 937-950
%D 2018
%X Diabetic nephropathy correlates more closely to defective mitochondria and increased oxidative stress in the kidney than to hyperglycemia. A key driving factor of diabetic nephropathy is angiotensin II acting via the G-protein-coupled cell membrane type 1 receptor. The present study aimed to investigate the role of the angiotensin II type 2 receptor (AT2R) at the early stages of diabetic nephropathy. Using receptor binding studies and immunohistochemistry we found that the mitochondria in renal tubules contain high-affinity AT2Rs. Increased renal mitochondrial AT2R density by transgenic overexpression was associated with reduced superoxide production of isolated mitochondria from non-diabetic rats. Streptozotocin-induced diabetes (28 days) caused a drop in the ATP/oxygen ratio and an increase in the superoxide production of isolated renal mitochondria from wild-type diabetic rats. This correlated with changes in the renal expression profile and increased tubular epithelial cell proliferation. AT2R overexpression in tubular epithelial cells inhibited all diabetes-induced renal changes including a drop in mitochondrial bioenergetics efficiency, a rise in mitochondrial superoxide production, metabolic reprogramming, and increased proliferation. Thus, AT2Rs translocate to mitochondria and can contribute to reno-protective effects at early stages of diabetes. Hence, targeted AT2R overexpression in renal cells may open new avenues to develop novel types of drugs preventing diabetic nephropathy.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:30190172
%R 10.1016/j.kint.2018.06.006
%U https://inrepo02.dkfz.de/record/137573