Renin and kallikrein in connecting tubule of mouse

Andreas Rohrwasser, Tomoaki Ishigami, Barbu Gociman, Pierre Lantelme, Terry Morgan, Tong Cheng, Elaine Hillas, Shuhua Zhang, Kenneth Ward, May Bloch-Faure, Pierre Meneton, J. M. Lalouel

Research output: Contribution to journalArticle

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Abstract

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, 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. 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.

Original languageEnglish (US)
Pages (from-to)2155-2162
Number of pages8
JournalKidney International
Volume64
Issue number6
DOIs
StatePublished - Dec 2003
Externally publishedYes

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Kallikreins
Renin
Tissue Kallikreins
In Situ Hybridization
Urine
Plasma Volume

Keywords

  • Connecting tubule
  • Kallikrein
  • Mouse
  • Nephron
  • Prorenin
  • Renin
  • Urinary excretion

ASJC Scopus subject areas

  • Nephrology

Cite this

Rohrwasser, A., Ishigami, T., Gociman, B., Lantelme, P., Morgan, T., Cheng, T., ... Lalouel, J. M. (2003). Renin and kallikrein in connecting tubule of mouse. Kidney International, 64(6), 2155-2162. https://doi.org/10.1046/j.1523-1755.2003.00302.x

Renin and kallikrein in connecting tubule of mouse. / Rohrwasser, Andreas; Ishigami, Tomoaki; Gociman, Barbu; Lantelme, Pierre; Morgan, Terry; Cheng, Tong; Hillas, Elaine; Zhang, Shuhua; Ward, Kenneth; Bloch-Faure, May; Meneton, Pierre; Lalouel, J. M.

In: Kidney International, Vol. 64, No. 6, 12.2003, p. 2155-2162.

Research output: Contribution to journalArticle

Rohrwasser, A, Ishigami, T, Gociman, B, Lantelme, P, Morgan, T, Cheng, T, Hillas, E, Zhang, S, Ward, K, Bloch-Faure, M, Meneton, P & Lalouel, JM 2003, 'Renin and kallikrein in connecting tubule of mouse', Kidney International, vol. 64, no. 6, pp. 2155-2162. https://doi.org/10.1046/j.1523-1755.2003.00302.x
Rohrwasser A, Ishigami T, Gociman B, Lantelme P, Morgan T, Cheng T et al. Renin and kallikrein in connecting tubule of mouse. Kidney International. 2003 Dec;64(6):2155-2162. https://doi.org/10.1046/j.1523-1755.2003.00302.x
Rohrwasser, Andreas ; Ishigami, Tomoaki ; Gociman, Barbu ; Lantelme, Pierre ; Morgan, Terry ; Cheng, Tong ; Hillas, Elaine ; Zhang, Shuhua ; Ward, Kenneth ; Bloch-Faure, May ; Meneton, Pierre ; Lalouel, J. M. / Renin and kallikrein in connecting tubule of mouse. In: Kidney International. 2003 ; Vol. 64, No. 6. pp. 2155-2162.
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abstract = "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, 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. 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.",
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AU - Rohrwasser, Andreas

AU - Ishigami, Tomoaki

AU - Gociman, Barbu

AU - Lantelme, Pierre

AU - Morgan, Terry

AU - Cheng, Tong

AU - Hillas, Elaine

AU - Zhang, Shuhua

AU - Ward, Kenneth

AU - Bloch-Faure, May

AU - Meneton, Pierre

AU - Lalouel, J. M.

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N2 - 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, 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. 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.

AB - 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, 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. 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.

KW - Connecting tubule

KW - Kallikrein

KW - Mouse

KW - Nephron

KW - Prorenin

KW - Renin

KW - Urinary excretion

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