Effect of the long-term treatment with trandolapril on endoglin expression in rats with experimental renal fibrosis induced by renal mass reduction.

Abstract

BACKGROUND:

Endoglin is a membrane glycoprotein that regulates TGF-beta1 signaling. Previous studies have revealed that endoglin is upregulated in several models of experimental fibrosis, and that endoglin expression can counteract the fibrogenic effects of TGF-beta1. As treatment with angiotensin converting enzyme (ACE) inhibitors reduces renal fibrosis by mechanisms that are, in part, not dependent on angiotensin II blockade, we have assessed the hypothesis that this effect could be mediated by endoglin upregulation.

METHODS:

We have used the 5/6-nephrectomy renal mass reduction (RMR) model of renal fibrosis in rats treated (RMR+T) or not treated with the ACE inhibitor trandolapril (0.7 mg/kg/day). One, 3 and 5 months after RMR, mean arterial pressure and renal function were measured. In addition, renal fibrosis was evaluated quantitatively and endoglin, TGF-beta1, collagen type I and collagen type IV expression was assessed by Northern blot and immunohistochemistry.

RESULTS:

RMR induced a progressive increase in mean arterial pressure, urinary protein excretion and glomerular and tubulointerstitial fibrosis, which is accompanied by an increased expression of TGF-beta1, endoglin and collagen types I and IV. Trandolapril treatment reduced systemic blood pressure and lessened proteinuria after RMR, as well as expression of TGF-beta1, endoglin and collagens.

CONCLUSION:

The present study demonstrates an increased TGF-beta1, endoglin, collagen type I and collagen type IV expression in rats with severe hypertension and renal damage. The effect of trandolapril to decrease renal fibrosis seems to be based in a reduced TGF-beta1 expression but not in an increased expression of endoglin.

• Authors: Marta Prieto, Ana Rodríguez-Peña, Miguel Arévalo, Juan V Rivas, Annette Düwel, Nélida Eleno, Rafael J Sánchez, Ana I Morales, José M López-Novoa, Fernando Pérez-Barriocanal
• Journal: Kidney & blood pressure research (Kidney Blood Press Res) Vol. 28 Issue 1 Pg. 32-40 ( 2005) ISSN: 1420-4096 [Print] Switzerland
• PMID: 15475654 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Endoglin
• Eng protein, rat
• Indoles
• Intracellular Signaling Peptides and Proteins
• Transforming Growth Factor beta
• trandolapril

Topics

• Angiotensin-Converting Enzyme Inhibitors (pharmacology)
• Animals
• Down-Regulation (drug effects)
• Endoglin
• Fibrosis (drug therapy, metabolism, pathology)
• Indoles (pharmacology)
• Intracellular Signaling Peptides and Proteins (metabolism)
• Kidney Diseases (drug therapy, metabolism, pathology)
• Male
• Rats
• Rats, Wistar
• Signal Transduction (drug effects)
• Time Factors
• Transforming Growth Factor beta (biosynthesis)
• Up-Regulation (drug effects)