Effect of TGF-β1 antisense oligodeoxynucleotide on renal function in chronic renal failure rats

Abstract

Aim: The aim of the present study was to investigate the effectiveness of transforming growth factor (TGF)-β1 antisense oligodeoxynucleotides (ODN) in ameliorating deteriorated kidney function in rats with puromycin-induced chronic renal failure (CRF). Methods: Saline, puromycin, puromycin+TGF-β1 antisense ODN or puromycin+scrambled ODN were administered to unilaterally nephrectomized rats. Renal hemodynamic and excretory measurements were taken in the anaesthetized rats that had undergone surgical procedure. Results: It was observed that in the CRF rats, there was a marked reduction in the renal blood flow (RBF), glomerular filtration rate (GFR), severe proteinuria, and almost 6-fold increased fractional excretion of sodium (FE Na + ) as compared to that in the control rats (all P<0.05). It was further observed that in the CRF rats, the treatment with TGF-β1 antisense, but not scrambled ODN, markedly attenuated the reduction of RBF, GFR, and proteinuria and markedly prevented the increase of the FE Na + (all P<0.05). In addition, the renal hypertrophy in the CRF group (P<0.05 vs non-renal failure control) was markedly attenuated after treatment with TGF-1 antisense ODN (P<0.05). Focal segmental glomerulosclerosis was evident only in the untreated and scrambled ODN-treated CRF groups. An interesting observation of this study was that in the CRF rats, although there was marked attenuating and preventive effects of the TGF-β1 antisense ODN on the deteriorated renal functions, the antisense treatment did not cause any marked change in the renal expression of TGF-β1 at the protein level. Conclusion: Collectively, the data obtained suggests that TGF-β1 antisense ODN possesses beneficial effects in puromycininduced chronic renal failure and that the deterioration in morphology and impaired renal function in this pathological state is in part dependent upon the action of TGF-β1 within the kidney.

Urinary transforming growth factor beta1 in children and adolescents with congenital solitary kidney

“…Even though TGF beta1 is typically known to be an inhibitor of cell growth, authors consider that it prevents only the synthesis of DNA and cell proliferation, but promotes mRNA and protein synthesis, therefore enhancing cell hypertrophy. Hiong et al [50] showed that, in rats, treatment of chronic renal failure with TGF beta1 antisense oligodeoxynucleotides (ODNs) prevented hypertrophy of the kidneys, probably due to the suppression of the extracellular matrix accumulation in the kidney. TGF beta1 antisense ODN treatment reduced kidney weight in diabetic mice with kidney hypertrophy [51].…”

Association of TGF-β1, IL-4, and IL-10 Polymorphisms With Chronic Kidney Disease Susceptibility: A Meta-Analysis

“…In CKD cats, urinary TGF-b1 levels (TGF-b1/creatinine ratio) were dramatically up-regulated and could be used as a clinical marker for disease progression (Arata et al, 2005). It was showed that impaired renal function and the deterioration in morphology was in part dependent upon the action of TGF-b1 within the kidney in CKD model rats (Hiong et al, 2008). Previous epidemiological studies implicated three common single nucleotide polymorphisms (SNPs) in the TGF-b1 gene, namely rs1800469 (C509T), rs1800470 (T869C), and rs1800471 (G915C) in the susceptibility to CKD.…”

Osthole protects against inflammation in a rat model of chronic kidney failure via suppression of nuclear factor-κB, transforming growth factor-β1 and activation of phosphoinositide 3-kinase/protein kinase B/nuclear factor (erythroid-derived 2)-like 2 signaling

“…As a transduction molecule, mothers against decapentaplegic (Smad) protein transduces TGF-β1 family signals to the nucleus. The TGF-β1/Smad pathway is a final and common pathway of renal fibrosis (24). In the TGF-β1/Smad signaling pathway, an active transcription complex produced by Smad2/3 enters the nucleus while Smad6 inhibits the transduction of TGF-β1 signals (25).…”