Renin and kallikrein in connecting tubule of mouse.
Renin and kallikrein in connecting tubule of mouse.
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小鼠连接小管中的肾素和激肽释放酶。
DOI：
10.1046/j.1523-1755.2003.00302.x
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
Lalouel,JM
中科院分区：
文献类型：
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作者：
Rohrwasser,Andreas;Ishigami,Tomoaki;Gociman,Barbu;Lantelme,Pierre;Morgan,Terry;Cheng,Tong;Hillas,Elaine;Zhang,Shuhua;Ward,Kenneth;Bloch-Faure,May;Meneton,Pierre;Lalouel,JM
肾素和激肽释放酶在小鼠连接小管中的表达背景肾素在连接小管中的表达，也是组织激肽释放酶(KLK-1)的表达片段，提出了两个问题。这些基因在连接小管的同一细胞还是不同细胞中表达？这种结构是否支持KLK-1激活前肾素的假说，或者更有可能是它提供了协调的基因调控？方法用免疫组织化学和原位杂交的方法检测肾素和KLK-1。体外研究KLK-1对肾素的激活作用。在体内，比较了靶向失活KLK-1(TK−/−)纯合子和正常产仔(TK+/+)纯合子小鼠的肾素原和活性肾素的排泄。我们证实了KLK-1在体外激活了原肾素，但TK-−/−和TK+/+动物的尿中活性肾素/原肾素的比值没有差异。与TK+/+对照组相比，TK−/−小鼠24小时尿量和活性肾素排泄量显著降低(5.05±1.16mgAng/h vs.9.39±1.96mgAng/h，P<；0.05)和活性肾素(1.98±0.25mgAng/hvs.3.58±0.39mgAng/h，P<；0.05)，尿量和血浆肾素浓度均无差异。相反，与TK+/+相比，TK−/−中活性肾素和前肾素的排泄量较低，提示这两种蛋白参与集合管功能的协调调节。
Renin and kallikrein in connecting tubule of mouse.BackgroundThe observation of renin expression in connecting tubule, a segment that also expresses tissue kallikrein (KLK-1), raises two questions. Are the genes expressed in the same or in different cells of connecting tubule? Does this topography support the hypothesis that KLK-1 activates prorenin or is it more likely that it affords coordinated gene regulation?MethodsRenin and KLK-1 were examined by immunostaining and in situ hybridization. Renin activation by KLK-1 was investigated in vitro. In vivo, excretion of prorenin and active renin was compared in mice homozygous for targeted inactivation of KLK-1 (TK−/−) and normal littermates (TK+/+).ResultsUsing in situ immunostaining for renin and in situ hybridization for KLK-1 mRNA, we found that connecting tubule cells expressing renin also expressed KLK-1. We confirmed in vitro activation of prorenin by KLK-1, but found no difference in the ratio of active renin to prorenin in urine of TK−/−and TK+/+animals. Compared to TK+/+controls, TK−/−mice exhibited significantly lower 24-hour excretion of prorenin (5.05 ± 1.16 mg Ang I/hour vs. 9.39 ± 1.96 mg Ang I/hour,P< 0.05) and active renin (1.98 ± 0.25 mg Ang I/hour vs. 3.58 ± 0.39 mg Ang I/hour,P< 0.05), with no difference in either urine volumes or plasma renin concentrations.ConclusionDirect interaction between renin and KLK-1, not ruled out in vitro, is not supported in vivo. By contrast, lower excretion of active renin and prorenin in TK−/−compared to TK+/+suggest coordinated regulation of the two proteins in their participation to collecting duct function.