Valsartan inhibited HIF-1α pathway and attenuated renal interstitial fibrosis in streptozotocin-diabetic rats.

Abstract

AIM:

To investigate the effect of angiotensin II AT1 receptor blocker valsartan on hypoxia-inducible factor (HIF)-1α-mediated gene activation and its association with renal interstitial fibrosis (RIF) in diabetic nephropathy rats.

METHODS:

Sprague-Dawley rats were randomly divided into 3 groups: control (C group), streptozocin-induced diabetic nephropathy (D group), and valsartan-treated D rats (T group). At end of the 4th, 8th and 12th week 6 rats from each group were sacrificed and blood, urine and kidneys were collected. Blood glucose, serum creatinine (Scr) and 24-h urinary protein were measured and kidneys were processed for Masson-stain as well as immunohistochemistry and real time-PCR analyses of the expressions of HIF-1α, and its target genes tissue inhibitor of metalloproteinase (TIMP)-1 and endothelin (ET)-1 in the kidney.

RESULT:

(1) At the 4th, 8th and 12th week, the areas of RIF were significantly increased in D and T groups, which was accompanied by higher levels of 24-h urinary protein, Scr, HIF-1α, ET-1 and TIMP-1 compared with C group. (2) At the 8th and 12th week, the above changes were significantly attenuated in T group compared with D group.

CONCLUSIONS:

Valsartan may reduce HIF-1α-mediated gene activation and consequently improve kidney damage in diabetic nephropathy rats.

• Authors: Lin Tang, Run Yi, Bing Yang, Hui Li, Huijuan Chen, Zhangsuo Liu
• Journal: Diabetes research and clinical practice (Diabetes Res Clin Pract) Vol. 97 Issue 1 Pg. 125-31 (Jul 2012) ISSN: 1872-8227 [Electronic] Ireland
• PMID: 22377232 (Publication Type: Journal Article)
• Copyright: Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Blood Glucose
• Endothelin-1
• Hif1a protein, rat
• Hypoxia-Inducible Factor 1, alpha Subunit
• Tetrazoles
• Tissue Inhibitor of Metalloproteinase-1
• Streptozocin
• Valsartan
• Creatinine
• Valine

Topics

• Animals
• Blood Glucose (metabolism)
• Blotting, Western
• Creatinine (blood)
• Diabetes Mellitus, Experimental (drug therapy, pathology)
• Diabetic Nephropathies (drug therapy, pathology)
• Endothelin-1 (metabolism)
• Gene Expression
• Hypoxia-Inducible Factor 1, alpha Subunit (antagonists & inhibitors, metabolism)
• Immunohistochemistry
• Kidney (drug effects, pathology)
• Male
• Nephritis, Interstitial (drug therapy, pathology)
• Proteinuria (metabolism)
• Rats
• Rats, Sprague-Dawley
• Real-Time Polymerase Chain Reaction
• Streptozocin
• Tetrazoles (pharmacology)
• Tissue Inhibitor of Metalloproteinase-1 (metabolism)
• Valine (analogs & derivatives, pharmacology)
• Valsartan