Role of angiotensin II in the expression and regulation of transforming growth factor-beta in obstructive nephropathy.

Role of angiotensin II in the expression and regulation of transforming growth factor-beta in obstructive nephropathy.
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血管紧张素II在阻塞性肾病转化生长因子-β的表达和调节中的作用。

DOI:
10.1038/ki.1995.407
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发表时间:
1995
影响因子:
19.6
通讯作者:
Martínez-Maldonado,M
Martínez-Maldonado,M
中科院分区:
医学1区
文献类型:
--
作者:
PimentelJr,JL;Sundell,CL;Wang,S;Kopp,JB;Montero,A;Martínez-Maldonado,M

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血管紧张素II在梗阻性肾病转化生长因子-β表达调控中的作用单侧输尿管梗阻(UUO)导致梗阻肾纤维化。我们验证了UUO间质纤维化的假设,即至少部分是由于转化生长因子-β(转化生长因子-β)的表达增强,而转化生长因子-DNA的表达又受局部血管紧张素II(Ang II)的产生调节。(一般名称转化生长因子-β用于讨论所有异构体共有的性质,但在特殊需要时特别提到其他异构体。)采用Northern印迹和免疫组织化学方法检测梗阻后24小时和1周大鼠肾脏转化生长因子-β的表达。与对侧和假肾相比,这两个时期的梗阻肾脏的间质和血管周围的转化生长因子-β免疫反应增强,后者的免疫染色仅限于内髓。AUUO组和CUUUO组梗阻大鼠肾组织中所有转化生长因子-β亚型的相对丰度均高于对侧和假手术侧。转化生长因子-β亚型的表达因梗阻部位(皮质与髓质)、肾单位节段、细胞类型和梗阻时间的不同而不同。氯沙坦可使AUUO和CUUO转化生长因子-β免疫反应性和表达水平的增加几乎完全消失。我们得出的结论是:(A)转化生长因子-β基因表达增加并受到差异调节;(B)血管紧张素转换酶II至少部分介导转化生长因子-β基因的过度表达;(C)血管紧张素转换酶II可能在本模型和其他肾小管间质疾病的纤维化形成中发挥中心作用。
Role of angiotensin II in the expression and regulation of transforming growth factor-β in obstructive nephropathy. Unilateral ureteral obstruction (UUO) leads to fibrosis of the obstructed kidney. We tested the hypothesis that interstitial fibrosis in UUO results, at least in part, from enhanced expression of transforming growth factor-β (TGF-β) which in turn is regulated by local angiotensin II (Ang II) generation. (The generic name TGF-β is used to discuss properties shared by all isoforms, but special reference to other isoforms is made when specifically needed.) Using Northern blot and immunohistochemical analysis, we examined the expression of TGF-β in rat kidneys after 24 hours (aUUO) and one week (cUUO) of obstruction. Obstructed kidneys from both periods had increased interstitial and perivascular TGF-β immunoreactivity compared to contralateral and sham kidneys, in which immunostaining was confined to the inner medulla. Relative abundance of all TGF-β mRNA isoforms were higher in the obstructed than in contralateral and sham kidneys in both aUUO and cUUO. Expression of TGF-β isoforms varied according to site (cortex vs. medulla), segment of the nephron, type of cells and duration of the obstruction. The increase in TGF-β immunoreactivity and mRNA levels in aUUO and cUUO was almost totally abolished by pretreatment with losartan. We conclude that in UUO: (a) TGF-β gene expression is increased and differentially regulated; (b) Ang II, at least partially, mediates the overexpression of TGF-β gene; and (c) Ang II may play a central role in fibrogenesis in this and other models of tubulointerstitial disease.
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