Angiotensin stimulates TGF-beta1 and clusterin in the hydronephrotic neonatal rat kidney.

Angiotensin stimulates TGF-beta1 and clusterin in the hydronephrotic neonatal rat kidney.
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血管紧张素刺激肾积水新生大鼠肾脏中的 TGF-β1 和簇蛋白。

DOI:
10.1152/ajpregu.2000.278.3.r640
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发表时间:
2000
期刊:
American journal of physiology. Regulatory, integrative and comparative physiology
影响因子:
--
通讯作者:
Chevalier,RL
Chevalier,RL
中科院分区:
--
文献类型:
--
作者:
Yoo,KH;Thornhill,BA;Chevalier,RL

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单侧输尿管梗阻 (UUO) 会诱导肾素-血管紧张素系统的激活以及转化生长因子-β1(TGF-β1;一种调节细胞粘附和纤维发生的细胞因子)和簇蛋白(一种响应细胞损伤而产生的糖蛋白)的上调。本研究旨在探讨 ANG II 对新生大鼠肾 TGF-β1 和簇蛋白的调节作用。动物在出生后 2 天接受 UUO,3 天后测量肾脏 TGF-β1 和簇蛋白 mRNA。将大鼠分为接受盐水载体、ANG、氯沙坦(AT1 受体抑制剂)或 PD-123319(AT2 受体抑制剂)的治疗组。 ANG 通过 AT1 受体刺激肾脏 TGF-β1 表达,这一反应与成人相似。相反,聚集蛋白的表达是通过 AT2 受体刺激的,这种反应与成人的反应不同,成人中 ANG 通过 AT1 受体抑制聚集蛋白的表达。我们推测,新生儿肾积水肾脏对 ANG II 的独特反应是由于发育中的肾脏中 AT2 受体占优势。
Unilateral ureteral obstruction (UUO) induces activation of the renin-angiotensin system and upregulation of transforming growth factor-β1 (TGF-β1; a cytokine modulating cellular adhesion and fibrogenesis) and clusterin (a glycoprotein produced in response to cellular injury). This study was designed to examine the regulation of renal TGF-β1 and clusterin by ANG II in the neonatal rat. Animals were subjected to UUO in the first 2 days of life, and renal TGF-β1 and clusterin mRNA were measured 3 days later. Rats were divided into treatment groups receiving saline vehicle, ANG, losartan (AT1receptor inhibitor), or PD-123319 (AT2receptor inhibitor). ANG stimulated renal TGF-β1 expression via AT1receptors, a response similar to that in the adult. In contrast, clusterin expression was stimulated via AT2receptors, a response differing from that in the adult, in which ANG inhibits clusterin expression via AT1receptors. We speculate that the unique response of the neonatal hydronephrotic kidney to ANG II is due to the preponderance of AT2receptors in the developing kidney.