Effect of TGF-beta 1 antisense oligodeoxynucleotide on renal function in chronic renal failure rats

Hiong, L.C. and Voon, K.L. and Abdullah, N.A. and Sattar, M.A. and Rahman, N.A. and Khan, A.H. and Johns, E.J. (2008) Effect of TGF-beta 1 antisense oligodeoxynucleotide on renal function in chronic renal failure rats. Acta Pharmacologica Sinica, 29 (4). pp. 451-457. ISSN 1671-4083, DOI https://doi.org/10.1111/j.1745-7254.2008.00772.x.

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Aim: The aim of the present study was to investigate the effectiveness of transforming growth factor (TGF)-beta 1 antisense oligodeoxynucleotides (ODN) in ameliorating deteriorated kidney function in rats with puromycin-induced chronic renal failure (CRF). Methods: Saline, puromycin, puromycin+TGF-beta 1 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-beta 1 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-beta 1 antisense ODN on the deteriorated renal functions, the antisense treatment did not cause any marked change in the renal expression of TGF-beta 1 at the protein level. Conclusion: Collectively, the data obtained suggests that TGF-beta 1 antisense ODN possesses beneficial effects in puromycin-induced 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-beta 1 within the kidney.

Item Type: Article
Additional Information:
Uncontrolled Keywords: Chronic renal failure, transforming growth factor-β1, antisense oligodeoxynucleotides, renal function
Subjects: R Medicine
Divisions: Faculty of Medicine
Depositing User: Ms Haslinda Lahuddin
Date Deposited: 11 Nov 2013 03:36
Last Modified: 11 Nov 2013 03:36
URI: http://eprints.um.edu.my/id/eprint/8526

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