Kaneto H, Morrissey J, Klahr S
Department of Medicine, Jewish Hospital of St. Louis, Washington University Medical Center, Missouri.
Kidney Int. 1993 Aug;44(2):313-21. doi: 10.1038/ki.1993.246.
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)
肾间质纤维化是慢性输尿管梗阻的常见后果。虽然几种细胞因子可能启动纤维化形成，但转化生长因子-β（TGF-β）被认为是主要的刺激因子。据报道，TGF-β1调节细胞外基质（ECM）合成，血栓素（Tx）刺激ECM蛋白合成，并且血管紧张素II（Ang II）增加大鼠主动脉平滑肌细胞中TGF-β1 mRNA的表达。因此，我们通过逆转录结合聚合酶链反应测量单侧输尿管梗阻（UUO）大鼠肾皮质中TGF-β1 mRNA的表达，以确定Ang II和/或Tx是否刺激TGF-β1 mRNA增加。UUO大鼠对侧肾脏中的TGF-β1 mRNA水平在梗阻14天期间没有显著变化，而在梗阻肾脏中，与对照（未手术大鼠）肾脏相比，三天后TGF-β1 mRNA水平显著增加。在梗阻肾脏皮质中TGF-β1 mRNA表达的增加见于肾小管细胞而非肾小球。血栓素合酶抑制剂OKY-046不影响梗阻肾脏中TGF-β1 mRNA的变化。血管紧张素I转换酶抑制剂依那普利显著减弱但未完全消除TGF-β1 mRNA的增加。这些数据表明，在梗阻中TGF-β1在转录水平增加，因此可能在梗阻性肾病的纤维化形成起始中起作用。血栓素对细胞外基质合成的作用似乎不是由TGF-β1介导的。（摘要截短于250字）
