Open AccessEffect of TGF‐β1 antisense oligodeoxynucleotide on renal function in chronic renal failure rats 1
Author(s) -
HIONG Law Chung,
VOON Kiew Lik,
ABDULLAH Nor Azizan,
SATTAR Munavvar A,
RAHMAN Nazarina Abdul,
KHAN Abdul Hye,
JOHNS Edward James
Publication year - 2008
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2008.00772.x
Subject(s) - chronic renal failure , transforming growth factor , renal function , medicine , endocrinology , kidney , function (biology) , chemistry , pharmacology , microbiology and biotechnology , biology
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 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‐β1 within the kidney.