Journal Article

DKFZ-2018-01453

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The angiotensin II type 2 receptors protect renal tubule mitochondria in early stages of diabetes mellitus.

Micakovic, T. ; Papagiannarou, S. ; Clark, E. ; Kuzay, Y. ; Abramovic, K. ; Peters, J. ; Sticht, C. ; Volk, N. ; Fleming, T. ; Nawroth, P. ; Hammes, H.-P. ; Alenina, N. ; Gröne, H.-J.DKFZ* ; Hoffmann, S. C.

2018
Nature Publishing Group Basingstoke

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Please use a persistent id in citations: doi:10.1016/j.kint.2018.06.006

Abstract: 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.

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Contributing Institute(s):

1. Zelluläre und Molekulare Pathologie (G130)

Research Program(s):

1. 322 - Genetics and Pathophysiology (POF3-322) (POF3-322)

Appears in the scientific report 2018

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Database coverage:
; BIOSIS Previews ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF >= 5 ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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