scholarly journals Transforming growth factor β1 and renal injury following subtotal nephrectomy in the rat: Role of the renin-angiotensin system

1997 ◽  
Vol 51 (5) ◽  
pp. 1553-1567 ◽  
Author(s):  
Leonard L. Wu ◽  
Alison Cox ◽  
Chris J. Roe ◽  
Marie Dziadek ◽  
Mark E. Cooper ◽  
...  
Keyword(s):  
Growth Factor ◽  
Renal Injury ◽  
Transforming Growth Factor ◽  
Renin Angiotensin System ◽  
Transforming Growth Factor Β1 ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Subtotal Nephrectomy

AT1 antagonism and renin inhibition in mice: pivotal role of targeting angiotensin II in chronic kidney disease

2012 ◽  
Vol 303 (7) ◽  
pp. F1037-F1048 ◽  
Author(s):  
Christoph Fraune ◽  
Sascha Lange ◽  
Christian Krebs ◽  
Alexandra Hölzel ◽  
Jana Baucke ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Injury ◽  
Plasma Concentrations ◽  
Renin Angiotensin System ◽  
Pivotal Role ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Renin Inhibition

The role of the renin-angiotensin system in chronic kidney disease involves multiple peptides and receptors. Exerting antipodal pathophysiological mechanisms, renin inhibition and AT1 antagonism ameliorate renal damage. However, it is unclear which mechanism exerts better nephroprotection. We compared the renin inhibitor aliskiren with the AT1 antagonist losartan in mice with chronic kidney disease due to renal ablation. Doses were adjusted to equipotent inhibition of the renin-angiotensin system, determined via a dose-response quantifying plasma and renal renin expression. Six-week treatment with either 500 mg/l drinking water losartan or 50 mg·kg−1·day−1 aliskiren significantly decreased albuminuria, glomerular damage, and transcription rates of renal injury markers to a similar extent. An array analysis comparing renal gene expression of losartan- and aliskiren-treated mice evaluating >34,000 transcripts demonstrated regulation for 14 genes only, with small differences. No superior nephroprotection was found by combining losartan and aliskiren. Compared with plasma concentrations, aliskiren accumulated ∼7- to 29-fold in the heart, liver, lung, and spleen and ∼156-fold in the kidney. After withdrawal, plasma concentrations dropped to zero within 24 h, whereas renal tissue concentrations declined slowly over days. Withdrawal of aliskiren in mice with chronic kidney disease revealed a significantly delayed re-increase in albuminuria compared with withdrawal of losartan. This study demonstrates equieffective nephroprotection of renin inhibition and AT1 antagonism in mice with chronic kidney disease without additional benefit of combination therapy. These observations underscore the pivotal role of targeting ANG II to reduce renal injury.

scholarly journals Secreted protein acidic and rich in cysteine expression after subtotal nephrectomy and blockade of the renin-angiotensin system.

1997 ◽  
Vol 8 (9) ◽  
pp. 1373-1382
Author(s):  
L L Wu ◽  
A Cox ◽  
C J Roe ◽  
M Dziadek ◽  
M E Cooper ◽  
...  
Keyword(s):  
Renal Injury ◽  
De Novo ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Secreted Protein ◽  
Matrix Remodeling ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Subtotal Nephrectomy ◽  
Gene And Protein Expression

Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix-associated protein with antiadhesive, antiproliferative, and matrix remodeling properties. SPARC gene and protein expression were investigated after subtotal nephrectomy (STNx), a model of noninflammatory progressive renal injury. In addition, the effect of blockade of the renin-angiotensin system by the angiotensin-converting enzyme inhibitor ramipril or by the angiotensin II receptor antagonist valsartan was examined. The STNx rats developed hypertension, proteinuria, and renal impairment. These changes were associated with a 2.4-fold increase in SPARC gene expression in STNx compared with SHAM kidneys (P < 0.001). In situ hybridization revealed increased SPARC mRNA in glomeruli and interstitial cells, as well as de novo expression by tubular epithelial cells at sites of renal injury. Immunofluorescence studies confirmed concordant changes in SPARC protein. Both ramipril and valsartan ameliorated renal injury and significantly reduced SPARC overexpression in the STNx animals. The findings of the present study suggest that SPARC, in the context of its known biological actions, may influence some of the pathological features associated with significant renal mass reduction.

scholarly journals Hyperglycemia activates the renin-angiotensin system and induces epithelial-mesenchymal transition in streptozotocin-induced diabetic kidneys

2018 ◽  
Vol 19 (3) ◽  
pp. 147032031880300 ◽  
Author(s):  
Chung-Ming Chen ◽  
Shu-Hui Juan ◽  
Hsiu-Chu Chou
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Renin Angiotensin System ◽  
Transforming Growth Factor Β ◽  
Angiotensin System ◽  
Kidney Fibrosis ◽  
Mesenchymal Transition ◽  
Renin Angiotensin ◽  
Factor Α

Introduction: The renin–angiotensin system and epithelial–mesenchymal transition play crucial roles in the development of kidney fibrosis. The connection between the renin–angiotensin system and transforming growth factor-β in epithelial–mesenchymal transition remains largely unknown. Materials and methods: We assessed oxidative stress, cytokine levels, renal morphology, profibrotic growth factor and renin–angiotensin system component expression, and cell-specific E- and N-cadherin expression in the kidneys of gerbils with streptozotocin-induced diabetes mellitus. Results: Animals in the experimental group received an intraperitoneal injection of streptozotocin to induce diabetes. The diabetic gerbil kidneys presented kidney injury, which was manifested as distorted glomeruli, necrosis of tubular cells, dilated tubular lumen, and brush border loss. Additionally, the diabetic gerbil kidneys exhibited significantly higher expressions of 8-hydroxy-2′-deoxyguanosine, nuclear factor-kB, toll-like receptor 4, tumor necrosis factor-α, transforming growth factor-β, connective tissue growth factor, α-smooth muscle actin, and N-cadherin and higher collagen deposition than did the control gerbil kidneys. Compared with the control kidneys, the diabetic gerbil kidneys exhibited significantly lower E-cadherin expression. These epithelial–mesenchymal transition characteristics were associated with an increase in renin–angiotensin system expression in the diabetic gerbils. Conclusions: We demonstrate that hyperglycemia activated the renin–angiotensin system, induced epithelial–mesenchymal transition, and contributed to kidney fibrosis in an experimental diabetes mellitus model.

The Role of the Renin-Angiotensin System in Cholesterol and Puromycin Mediated Renal Injury

2002 ◽  
Vol 324 (6) ◽  
pp. 296-304 ◽  
Author(s):  
Siddhartha Ghosh ◽  
Domenic Sica ◽  
Anton C. Schoolwerth ◽  
Itaf Fakhry ◽  
Todd W.B. Gehr ◽  
...  
Keyword(s):  
Renal Injury ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin
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