TY - JOUR
T1 - Increased expression of TGF-β1 mRNA in the obstructed kidney of rats with unilateral ureteral ligation
AU - Kaneto, Hiroyuki
AU - Morrissey, Jerry
AU - Klahr, Saulo
N1 - Funding Information:
This work was supported by NIH Grants DK40321 and DK09976. The authors gratefully acknowledge the editorial assistance of Mr.
PY - 1993/8
Y1 - 1993/8
N2 - 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-βl 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-βl mRNA. TGF-β1 mRNA levels in 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 extracellular matrix synthesis does not appear to be mediated by TGF-β1. Angiotensin II has a role in stimulating TGF-β1 expression in UUO.
AB - 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-βl 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-βl mRNA. TGF-β1 mRNA levels in 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 extracellular matrix synthesis does not appear to be mediated by TGF-β1. Angiotensin II has a role in stimulating TGF-β1 expression in UUO.
UR - http://www.scopus.com/inward/record.url?scp=0027165757&partnerID=8YFLogxK
U2 - 10.1038/ki.1993.246
DO - 10.1038/ki.1993.246
M3 - Article
C2 - 8377375
AN - SCOPUS:0027165757
SN - 0085-2538
VL - 44
SP - 313
EP - 321
JO - Kidney International
JF - Kidney International
IS - 2
ER -