Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation
Gene targeting in mice reveals a requirement for angiotensin in the development and maintenance of kidney morphology and growth factor regulation
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DOI：
10.1172/jci118366
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发表时间：
1995-12-01
影响因子：
15.9
通讯作者：
Ichikawa, I
中科院分区：
文献类型：
--
作者：
Niimura, F;Labosky, PA;Ichikawa, I
内源性血管紧张素水平升高可导致高血压性肾硬化，这是由于肽的强效血管加压作用。我们通过基因靶向产生了血管紧张素原基因（Atg（-/-））无效突变的纯合子小鼠。出生后，Atg（-/-）动物表现出肾小球成熟的适度延迟，尽管Atg（-/-）动物在7周龄时是肿胀的，但在3周龄时，它们在肾皮质中发展出明显的病变，类似于高血压肾硬化症的病变。此外，纯合突变肾的乳头大小减小。这些病变伴随着皮质中PDGF-B和TGF-β 1 mRNA的局部上调和乳头中PDGF-A mRNA的下调。该研究表明，血管紧张素在实现和维持肾脏的正常形态中是重要的要求。血管紧张素维持哺乳动物体内体积稳态的机制包括促进乳头的成熟生长。
Elevated levels of endogenous angiotensin can cause hypertensive nephrosclerosis as a result of the potent vasopressor action of the peptide, We have produced by gene targeting mice homozygous for a null mutation in the angiotensinogen gene (Atg(-/-)). Postnatally, Atg(-/-) animals show a modest delay in glomerular maturation, Although Atg(-/-) animals are hypotensive by 7 wk of age, they develop, by 3 wk of age, pronounced lesions in the renal cortex, similar to those of hypertensive nephrosclerosis, In addition, the papillae of homozygous mutant kidneys are reduced in size. These lesions are accompanied by local up-regulation of PDGF-B and TGF-beta 1 mRNA in the cortex and down-regulation of PDGF-A mRNA in the papilla, The study demonstrates an important requirement for angiotensin in achieving and maintaining the normal morphology of the kidney. The mechanism through which angiotensin maintains the volume homeostasis in mammals includes promotion of the maturational growth of the papilla.