Renal mRNA expression of renin, AT-1 receptor, TGF-beta-1 and fibronectin in obstructive nephropathy

ABSTRACT

The present study was designed to quantify the alterations of renal renin, angiotensin type I receptor (AT-1), TGF-beta-1, and fibronectin gene expression in rats with unilateral ureteral obstruction (UUO). We also investigated the change of AT-1 density during UUO. Reverse transcription-polymerase chain reaction (RT-PCR) technique and receptor binding assay were used to detect mRNA expression and receptor density, respectively. At one day after UUO, renin mRNA level of the obstructed kidneys was decreased transiently and then subsequently increased to the level of sham kidneys. In the contralateral kidneys of the same rats, on the contrary, renin mRNA level was gradually decreased. Then, at 9 days after UUO, it was significantly lower than that of sham kidneys. The expressions of both AT-1 subtypes, called AT-1A and AT-1B, mRNAs did not change at any time. UUO led to a significant decrease in AT-1 density in the obstructed kidneys compared with the sham kidneys at 1 and 3 days (66 +/- 11.6% (p lt 0.05) and 73 +/- 4.0% (p lt 0.01), respectively). Thereafter, AT-1 density was gradually increased and at 9 days it showed a marked elevation in the obstructed kidneys compared to the sham kidneys. In contrast, in the contralateral kidneys AT-1 density was significantly reduced from 3 to 9 days after UUO. The TGF-beta-1 m-RNA level of the obstructed kidneys was unexpectedly decreased at 6 days after UUO. Then, at 9 days it was followed by a significant increase in the obstructed kidneys, whereas it showed an obvious decrease in the contralateral kidneys. In addition, fibronectin mRNA level was also significantly increased in the obstructed kidneys after UUO compared to the sham or the contralateral kidneys of the same rats. These results suggest a differential regulation of renal renin, AT-1 receptor, TGF-beta-1 and fibronectin mRNA levels at different stages of UUO.