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.
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.
Authors: Eric W Brunskill; Maria Luisa S Sequeira-Lopez; Ellen S Pentz; Eugene Lin; Jing Yu; Bruce J Aronow; S Steven Potter; R Ariel Gomez Journal: J Am Soc Nephrol Date: 2011-10-27 Impact factor: 10.121
Authors: Maria Luisa S Sequeira-Lopez; Vidya K Nagalakshmi; Minghong Li; Curt D Sigmund; R Ariel Gomez Journal: Am J Physiol Regul Integr Comp Physiol Date: 2015-08-05 Impact factor: 3.619
Authors: Alexis A Gonzalez; Liu Liu; Lucienne S Lara; Dale M Seth; L Gabriel Navar; Minolfa C Prieto Journal: Hypertension Date: 2011-01-31 Impact factor: 10.190
Authors: Nirupama Ramkumar; Deborah Stuart; Elena Mironova; Nikita Abraham; Yang Gao; Shuping Wang; Jayalakshmi Lakshmipathi; James D Stockand; Donald E Kohan Journal: Am J Physiol Renal Physiol Date: 2018-05-23
Authors: Alison C Berg; Catalina Chernavvsky-Sequeira; Jennifer Lindsey; R Ariel Gomez; Maria Luisa S Sequeira-Lopez Journal: World J Nephrol Date: 2013-02-06
Authors: Nirupama Ramkumar; Deborah Stuart; Matias Calquin; Syed Quadri; Shuping Wang; Alfred N Van Hoek; Helmy M Siragy; Atsuhiro Ichihara; Donald E Kohan Journal: Am J Physiol Renal Physiol Date: 2015-05-20
Authors: Nirupama Ramkumar; Deborah Stuart; Sara Rees; Alfred Van Hoek; Curt D Sigmund; Donald E Kohan Journal: Am J Physiol Renal Physiol Date: 2014-08-13
Authors: Omar Guessoum; Alexandre de Goes Martini; Maria Luisa S Sequeira-Lopez; R Ariel Gomez Journal: Trends Mol Med Date: 2020-11-05 Impact factor: 11.951