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| Item Type: | Article |
|---|---|
| Title: | The angiotensin II type 2 receptors protect renal tubule mitochondria in early stages of diabetes mellitus |
| Creators Name: | 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. and Hoffmann, S.C. |
| 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. |
| Keywords: | Angiotensin, Diabetic Nephropathy, Mitochondria, Oxidative Stress, Animals, Mice, Rats |
| Source: | Kidney International |
| ISSN: | 0085-2538 |
| Publisher: | Elsevier |
| Volume: | 94 |
| Number: | 5 |
| Page Range: | 937-950 |
| Date: | November 2018 |
| Official Publication: | https://doi.org/10.1016/j.kint.2018.06.006 |
| PubMed: | View item in PubMed |
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