Increased expression of TGF-β1 mRNA in the obstructed kidney of rats with unilateral ureteral ligation

Kaneto, Hiroyuki; Morrissey, Jerry; Klahr, Saulo
August 1993
Kidney International;Aug1993, Vol. 44 Issue 2, p313
Academic Journal
Renal interstitial fibrosis is a common consequence of chronic ureteral obstruction. While several cytokines may initiate fibrogenesis, TGF-β is considered to be a major stimulating factor. It has been reported that TGF-β1 regulates extracellular matrix (ECM) synthesis, that thromboxane (Tx) stimulates ECM protein synthesis, and that angiotensin II (Ang II) increases expression of TGF-β1 mRNA in rat aortic smooth muscle cells. Therefore, we measured TGF-β1 mRNA expression by reverse transcription coupled with polymerase chain reaction in renal cortex of rats with unilateral ureteral obstruction (UUO) to determine whether Ang II and/or Tx stimulates increases in TGF-β1 mRNA. TGF-β1 mRNA levels m contralateral kidneys of rats with UUO did not change significantly during 14 days of obstruction, while in the obstructed kidney TGF-β1 mRNA levels were increased significantly after three days as compared to the control (unoperated rats) kidneys. The increase in TGF-β1 mRNA expression in the obstructed kidney cortex was found in tubular cells rather than glomeruli. OKY-046, an inhibitor of thromboxane synthase, did not affect the changes in TGF-β1 mRNA in the obstructed kidney. Enalapril, an angiotensin I converting enzyme inhibitor, significantly blunted but did not completely abrogate the increase in TGF-β1 mRNA. These data suggest that in obstruction TGF-β1 is increased at the transcriptional level and thus may play a role in initiating fibrogenesis in obstructive nephropathy. The effect of thromboxane on extra cellular matrix synthesis does not appear to be mediated by TGF-β1. Angiotensin II has a role m stimulating TGF-β1 expression in UUO.


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