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- Title
VASCULAR BIOLOGY – HEMODYNAMICS – HYPERTENSION Renin and kallikrein in connecting tubule of mouse.
- Authors
Rohrwasser, Andreas; Ishigami, Tomoaki; Gociman, Barbu; Lantelme, Pierre; Morgan, Terry; Tong Cheng; Hillas, Elaine; Shuhua Zhang; Ward, Kenneth; Bloch-Faure, May; Meneton, Pierre; Lalouel, J.M.
- Abstract
Renin and kallikrein in connecting tubule of mouse. Background. The 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? Methods. Renin 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+/+). Results. Using 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, ) and active renin (1.98 ± 0.25 mg Ang I/hour vs. 3.58 ± 0.39 mg Ang I/hour, ), with no difference in either urine volumes or plasma renin concentrations. Conclusion. Direct 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.
- Subjects
RENIN; KALLIKREIN; KIDNEY tubules; GENE expression
- Publication
Kidney International, 2003, Vol 64, Issue 6, p2155
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2003.00302.x