Ontogeny of renin and AT1 receptor in the rat

Ontogeny of renin and AT1 receptor in the rat
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大鼠肾素和AT1受体的个体发育

DOI:
10.1007/bf00852571
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发表时间:
1993
影响因子:
3
通讯作者:
E. Pentz
E. Pentz
中科院分区:
医学3区
文献类型:
--
作者:
R. A. Gomez;A. Tufro;A. Everett;E. Pentz

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肾素酶和血管紧张素 II (Ang II)、I 亚型受体 (ATI) 以组织特异性方式进行发育调节。在生命早期,肾素沿着肾血管系统广泛表达。随着成熟的进展,肾素 mRNA 水平下降,肾素靠近肾小球的定位发生变化。此外,新生大鼠中肾素分泌细胞的数量高于成年大鼠。新生儿和成人细胞暴露于 Ang II 会导致肾素分泌细胞数量出现类似程度的减少。这些发现表明,在未成熟动物中观察到的高水平肾素是由于肾素合成和释放增加而不是对血管紧张素II的反应减弱所致。 ATI 基因的表达也以组织特异性方式进行发育调节。随着成熟,ATI mRNA 水平在肾脏中降低,而在肝脏中升高。 ATI 转录物在肾源皮质前体细胞中的定位表明该受体在肾单位生长和发育中的作用。用 DUP753 抑制 ATI 会导致肾脏和体细胞生长延迟、肾素 mRNA 水平增加以及含肾素细胞的募集。这些观察结果表明,Ang II 通过 ATI 受体亚型对肾素基因表达产生强直负反馈。需要进一步的研究来描述介导这些发育变化的分子和细胞信号。
The enzyme renin and the angiotensin II (Ang II), subtype I receptor (ATI) are developmentally regulated in a tissue-specific manner. In early life, renin is expressed widely along the renal vasculature. As maturation progresses, there is a decrease in renin mRNA levels and a shift in the localization of renin close to the glomerulus. In addition, in the newborn rat, the number of renin-secreting cells is higher than in the adult rat. Exposure of neonatal and adult cells to Ang II results in a decrease of similar magnitude in the number of renin-secreting cells. These findings suggest that the high levels of renin observed in immature animals are due to increased renin synthesis and release rather than to a blunted response to Ang II. Expression of the ATI gene is also developmentally regulated in a tissue-specific manner. With maturation, ATI mRNA levels decrease in the kidney while they increase in the liver. The localization of ATI transcripts in precursor cells of the nephrogenic cortex suggests a role for this receptor in nephron growth and development. Inhibition of ATI with DUP753 results in delayed kidney and somatic growth and in increased renin mRNA levels and recruitment of renin-containing cells. These observations suggest that Ang II exerts a tonic negative feedback on renin gene expression via the ATI receptor subtype. Further studies are necessary to delineate the molecular and cellular signals mediating these developmental changes.
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发表时间: 1993
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