| Abstract | The intrarenal renin-angiotensin system (RAS) plays an important role in the progression of diabetic nephropathy. We have previously reported that mice overexpressing angiotensinogen in renal proximal tubular cells (RPTC) develop hypertension, albuminuria, and renal injury. Here, we investigated whether activation of the intrarenal RAS contributes to apoptosis of RPTC in diabetes. Induction of diabetes with streptozotocin in these transgenic mice led to significant increases in BP, albuminuria, RPTC apoptosis, and proapoptotic gene expression compared with diabetic nontransgenic littermates. Insulin and/or RAS blockers markedly attenuated these changes. Hydralazine prevented hypertension but not albuminuria, RPTC apoptosis, or proapoptotic gene expression. In vitro, high-glucose medium significantly increased apoptosis and caspase-3 activity in rat immortalized RPTC overexpressing angiotensinogen compared with control cells, and these changes were prevented by insulin and/or RAS blockers. In conclusion, intrarenal RAS activation and high glucose may act in concert to increase tubular apoptosis in diabetes, independent of systemic hypertension. |
| Authors | Fang Liu, Marie-Luise Brezniceanu, Chih-Chang Wei, Isabelle Chénier, Sébastien Sachetelli, Shao-Ling Zhang, Janos G Filep, Julie R Ingelfinger, John S D Chan
(Affiliation: Université de Montréal Centre hospitalier de l'Université de Montréal-Hôtel-Dieu, Research Centre Pavillon Masson, 3850 Saint Urbain Street, Montreal, Quebec, Canada H2W 1T8.)
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| Journal | Journal of the American Society of Nephrology : JASN
(J Am Soc Nephrol)
Vol. 19
Issue 2
Pg. 269-80
(Feb 2008)
ISSN: 1533-3450 United States |
| PMID | 18057217
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Antihypertensive Agents
- Bax protein, mouse
- Bcl2l1 protein, mouse
- Blood Glucose
- Hypoglycemic Agents
- bcl-2-Associated X Protein
- bcl-X Protein
- Angiotensinogen
- Insulin
- Losartan
- Perindopril
- Hydralazine
|
| Topics |
- Albuminuria
(drug therapy, pathology, physiopathology)
- Angiotensinogen
(genetics, physiology)
- Animals
- Antihypertensive Agents
(pharmacology)
- Apoptosis
(physiology)
- Blood Glucose
(metabolism)
- Cell Line, Transformed
- Diabetes Mellitus, Experimental
(drug therapy, pathology, physiopathology)
- Diabetic Nephropathies
(drug therapy, pathology, physiopathology)
- Hydralazine
(pharmacology)
- Hypertension, Renal
(drug therapy, pathology, physiopathology)
- Hypoglycemic Agents
(pharmacology)
- Insulin
(pharmacology)
- Kidney Tubules, Proximal
(pathology, physiology)
- Losartan
(pharmacology)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Perindopril
(pharmacology)
- Rats
- Renin-Angiotensin System
(physiology)
- bcl-2-Associated X Protein
(genetics)
- bcl-X Protein
(genetics)
|
