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Published on: July 3, 2013
Effect of TGF-beta1 antisense oligodeoxynucleotide on renal function in chronic renal failure rats
Law Chung Hiong1, Kiew Lik Voon, Nor Azizan Abdullah
1Department of Pharmacology, University of Malaya, Kuala Lumpur 50603, Malaysia.
Aim:
The aim of the present study was to investigate the effectiveness of transforming growth factor (TGF)-beta1 antisense oligodeoxynucleotides (ODN) in ameliorating deteriorated kidney function in rats with puromycin-induced chronic renal failure (CRF).
Methods:
Saline, puromycin, puromycin+TGF-beta1 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-beta1 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-beta1 antisense ODN on the deteriorated renal functions, the antisense treatment did not cause any marked change in the renal expression of TGF-beta1 at the protein level.
Conclusion:
Collectively, the data obtained suggests that TGF-beta1 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-beta1 within the kidney.
Insights
Transforming growth factor (TGF)-beta1 antisense oligodeoxynucleotides (ODN) improved kidney function in rats with chronic renal failure (CRF). This treatment attenuated renal dysfunction and morphological damage, suggesting TGF-beta1
Area of Science:
- Nephrology
- Molecular Biology
- Pharmacology
Background:
- Chronic renal failure (CRF) is characterized by progressive kidney damage and impaired function.
- Puromycin-induced nephropathy serves as a model for studying CRF.
- Transforming growth factor (TGF)-beta1 plays a role in renal fibrosis and disease progression.
Purpose of the Study:
- To evaluate the therapeutic efficacy of TGF-beta1 antisense oligodeoxynucleotides (ODN) in a rat model of puromycin-induced CRF.
- To assess the impact of TGF-beta1 antisense ODN on renal hemodynamics, excretory function, and kidney morphology.
- To determine if TGF-beta1 protein expression is altered by antisense treatment.
Main Methods:
- Rats underwent unilateral nephrectomy followed by puromycin administration to induce CRF.
- Treatment groups included saline, puromycin alone, puromycin + TGF-beta1 antisense ODN, and puromycin + scrambled ODN.
- Renal blood flow (RBF), glomerular filtration rate (GFR), proteinuria, fractional sodium excretion (FE Na+), and renal hypertrophy were measured.
Main Results:
- CRF rats exhibited reduced RBF and GFR, severe proteinuria, and increased FE Na+ compared to controls.
- TGF-beta1 antisense ODN treatment significantly improved RBF, GFR, reduced proteinuria, and prevented FE Na+ increase.
- Antisense treatment attenuated renal hypertrophy and prevented focal segmental glomerulosclerosis, without altering renal TGF-beta1 protein levels.
Conclusions:
- TGF-beta1 antisense ODN demonstrates significant renoprotective effects in puromycin-induced CRF.
- The study suggests that TGF-beta1 contributes to the morphological and functional deterioration in CRF.
- Targeting TGF-beta1 may represent a viable therapeutic strategy for chronic kidney disease.
