Increased expression of TGF-beta 1 mRNA in the obstructed kidney of rats with unilateral ureteral ligation.
Renal interstitial fibrosis is a common consequence of chronic ureteral obstruction. While several cytokines may initiate fibrogenesis, TGF-beta is considered to be a major stimulating factor. It has been reported that TGF-beta 1 regulates extracellular matrix (ECM) synthesis, that thromboxane (Tx) stimulates ECM protein synthesis, and that angiotensin II (Ang II) increases expression of TGF-beta 1 mRNA in rat aortic smooth muscle cells. Therefore, we measured TGF-beta 1 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-beta 1 mRNA. TGF-beta 1 mRNA levels in contralateral kidneys of rats with UUO did not change significantly during 14 days of obstruction, while in the obstructed kidney TGF-beta 1 mRNA levels were increased significantly after three days as compared to the control (unoperated rats) kidneys. The increase in TGF-beta 1 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-beta 1 mRNA in the obstructed kidney. Enalapril, an angiotensin I converting enzyme inhibitor, significantly blunted but did not completely abrogate the increase in TGF-beta 1 mRNA. These data suggest that in obstruction TGF-beta 1 is increased at the transcriptional level and thus may play a role in initiating fibrogenesis in obstructive nephropathy. The effect of thromboxane on extracellular matrix synthesis does not appear to be mediated by TGF-beta 1.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Medicine, Jewish Hospital of St. Louis, Washington University Medical Center, Missouri.
H
H
Kaneto
J
J
Morrissey
S
S
Klahr
D000818:Animals; D001483:Base Sequence; D004656:Enalapril / Q000494:pharmacology; D005260:Female; D005353:Fibronectins / Q000235:genetics; D007668:Kidney / Q000378:metabolism*; D008026:Ligation; D008689:Methacrylates / Q000494:pharmacology; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014517:Ureteral Obstruction / Q000378:metabolism*
D005353:Fibronectins; D008689:Methacrylates; D015335:Molecular Probes; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D004656:Enalapril; C034364:ozagrel