Renin and kallikrein in connecting tubule of mouse
Open accessAbstract
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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Candidate CNT cells were identified as a cluster overexpressing Calb1 and Klk1 genes.
“Candidate CNT cells were identified as a cluster overexpressing Calb1 and Klk1 genes [34, 56].”
From Systematic assessment of tissue dissociation and storage biases in single-cell and single-nucleus RNA-seq workflows (2020) · cites this paper as [56]
Cites
Ménard, J., & Catt, K. J. (1972) · Endocrinology · doi:10.1210/endo-90-2-422 · Cited by 456 · see citing works
Regulation of Intrarenal Angiotensin II in Hypertension
Navar, L. G., Harrison‐Bernard, L. M., Nishiyama, A., & Kobori, H. (2002) · Hypertension · doi:10.1161/hy0202.103821 · Cited by 375 · see citing works
Elements of a Paracrine Tubular Renin-Angiotensin System Along the Entire Nephron
Rohrwasser, A., Morgan, T. K., Dillon, H. F., Zhao, L., Callaway, C. W., Hillas, E., Zhang, S., Cheng, T., Inagami, T., Ward, K. J., et al. (1999) · Hypertension · doi:10.1161/01.hyp.34.6.1265 · Cited by 291 · see citing works
Self-citationProrenin and Other Large Molecular Weight Forms of Renin*
Sealey, J. E., Atlas, S. A., & Laragh, J. H. (1980) · Endocrine Reviews · doi:10.1210/edrv-1-4-365 · Cited by 232 · see citing works
Sealey, J. E., Atlas, S. A., Laragh, J. H., et al. (1978) · Nature · doi:10.1038/275144a0 · Cited by 188 · see citing works
Angiotensin II and long-term arterial pressure regulation: the overriding dominance of the kidney.
Hall, J. E., BRANDS, M., & Henegar, J. R. (1999) · PubMed · Cited by 185 · see citing works
Cardiovascular abnormalities with normal blood pressure in tissue kallikrein-deficient mice
Meneton, P., Bloch-Faure, M., Hagège, A. A., Ruetten, H., Huang, W., Bergaya, S., Ceiler, D. L., Gehring, D., Martins, I., Salmon, G., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.051619598 · Cited by 158 · see citing works
Self-citationSodium regulation of angiotensinogen mRNA expression in rat kidney cortex and medulla.
Ingelfinger, J. R., Pratt, R. E., Ellison, K., & Dzau, V. J. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112716 · Cited by 154 · see citing works
Altered Urinary Kallikrein Excretion in Rats with Hypertension
Margolius, H. S., Geller, R. G., de Jong, W., et al. (1972) · Circulation Research · doi:10.1161/01.res.30.3.358 · Cited by 149 · see citing works
Site of kininogenase secretion in the dog nephron
Scicli, A. G., Carretero, O. A., Hampton, A., et al. (1976) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1976.230.2.533 · Cited by 118 · see citing works
Bindels, R. J. M., Hartog, A., Timmermans, J., et al. (1991) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.1991.261.5.f799 · Cited by 116 · see citing works
Omata, K., Carretero, O. A., Scicli, A. G., et al. (1982) · Kidney International · doi:10.1038/ki.1982.218 · Cited by 107 · see citing works
Effects of Dietary Sodium and Genetic Background on Angiotensinogen and Renin in Mouse
Lantelme, P., Rohrwasser, A., Gociman, B. R., et al. (2002) · Hypertension · doi:10.1161/01.hyp.0000016177.20565.a0 · Cited by 105 · see citing works
Self-citationImmunoreactive kallikrein localization in the rat kidney: an immuno-electron-microscopic study.
Figueroa, C. D., Caorsi, I., Subiabre, J., et al. (1984) · Journal of Histochemistry & Cytochemistry · doi:10.1177/32.1.6558105 · Cited by 104 · see citing works
Localisation of immunoreactive kininogen and tissue kallikrein in the human nephron
Figueroa, C. D., MacIver, A. G., Mackenzie, J. C., & Bhoola, K. D. (1988) · Histochemistry and Cell Biology · doi:10.1007/bf00492599 · Cited by 103 · see citing works
Subcellular localization of renal kallikrein by ultrastructural immunocytochemistry
Vio, C. P., & Figueroa, C. D. (1985) · Kidney International · doi:10.1038/ki.1985.115 · Cited by 90 · see citing works
Evidence for a stimulatory effect of high potassium diet on renal kallikrein
Vio, C. P., & Figueroa, C. D. (1987) · Kidney International · doi:10.1038/ki.1987.146 · Cited by 86 · see citing works
Urinary kallikrein excretion in hypertension.
Margolius, H. S., Geller, R. G., De Jong, W., et al. (1972) · PubMed · Cited by 58 · see citing works
Activation of Inactive Plasma Renin by Plasma and Tissue Kallikreins
Derkx, F. H. M., Tan-Tjiong, H. L., Veld, A. J. M. I. '., et al. (1979) · Clinical Science · doi:10.1042/cs0570351 · Cited by 51 · see citing works
Vio, C. P., Loyola, S., & Velarde, V. (1992) · Hypertension · doi:10.1161/01.hyp.19.2_suppl.ii10 · Cited by 43 · see citing works
Cryoactivation and tryptic activation of blood 'prorenin' in normal man and animals
Osmond, D. H., & Cooper, R. M. (1978) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y78-125 · Cited by 42 · see citing works
Activation of Inactive Plasma Renin by Tissue Kallikreins*
Derkx, F. H. M., Tan-Tjiong, H. L., Veld, A. J. M. I., Schalekamp, M., & Schalekamp, M. A. D. H. (1979) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-49-5-765 · Cited by 37 · see citing works
Flow cytometric immunodissection of the human distal tubule and cortical collecting duct system
Helbert, M. J. F., Dauwe, S. E. H., & Broe, M. E. D. (2001) · Kidney International · doi:10.1046/j.1523-1755.2001.059002554.x · Cited by 36 · see citing works
Schalekamp, M. A. D. H., & Derkx, F. H. M. (1981) · Clinical Science · doi:10.1042/cs0610015 · Cited by 35 · see citing works
Rapid and large-scale purification and characterization of renin from mouse submaxillary gland
Misono, K. S., Holladay, L. A., Murakami, K., et al. (1982) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(82)90539-2 · Cited by 33 · see citing works
Observations on the Origin of Renin in Human Urine
Lumbers, E. R., & Skinner, S. L. (1969) · Circulation Research · doi:10.1161/01.res.24.5.689 · Cited by 26 · see citing works
Mechanism of the dipsogenic action of tetradecapeptide renin substrate
Simpson, J. B., Reid, I. A., Ramsay, D. J., et al. (1978) · Brain Research · doi:10.1016/0006-8993(78)90996-4 · Cited by 18 · see citing works
Morphologische Merkmale transportierender Epithelien
Kriz, W., Kaissling, B., Schiller, A., et al. (1979) · Journal of Molecular Medicine · doi:10.1007/bf01479982 · Cited by 18 · see citing works
Leyssac, P. P. (1978) · Kidney & Blood Pressure Research · doi:10.1159/000172660 · Cited by 16 · see citing works
Haley, W. E., & Johnson, J. W. (2008) · The Nephron journals/Nephron journals · doi:10.1159/000181237 · Cited by 12 · see citing works
Renin Activity in Urine, Plasma, and Renal Cortex of Dogs During Changes in Sodium Balance
Hayduk, K., Boucher, R., & Genest, J. J. (1971) · Experimental Biology and Medicine · doi:10.3181/00379727-136-35273 · Cited by 7 · see citing works
Urinary excretion of renin in the dog: effect of changes in plasma renin.
Bailie, M. D., Donoso, V. S., & Porter, T. (1983) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)33598-6 · Cited by 6 · see citing works
Purification of renin: a review.
Haber, E., & Slater, E. E. (1977) · PubMed · Cited by 6 · see citing works
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Denisenko, E., Guo, B. B., Jones, M., Hou, R., de Kock, L., Lassmann, T., Poppe, D., Clément, O., Simmons, R. K., Lister, R., et al. (2020) · Genome Biology · doi:10.1186/s13059-020-02048-6 · Cited by 686 · see citing works
- Authors
- Rohrwasser, A., Ishigami, T., Gociman, B., Lantelme, P., Morgan, T., Cheng, T., Hillas, E., Zhang, S., Ward, K., Bloch-Faure, M. A. Y., Meneton, P., & Lalouel, J. M.
- Affiliations
- University of Utah (US)
- Corresponding author
- Lalouel, J.M.
- Venue
- Kidney International
- Publisher
- Elsevier BV
- Published
- 2003-12
- Volume
- 64
- Issue
- 6
- Pages
- 2155-2162
- ISSN
- 0085-2538 (ISSN-L)
- OpenAlex
- W1985546355
- Cited by
- 64
- References
- 33
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2022: 3 · 2021: 1 · 2020: 4 · 2018: 2 · 2017: 2 · 2016: 1 · 2015: 7 · 2014: 6 · 2013: 5 · 2012: 4
- FWCI
- 1.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Kidney International (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ipsen
- National Institutes of Health (5r01hl045325-13)
- National Heart, Lung, and Blood Institute (HL55000, HL 45325, P50HL055000)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Genetics › Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Keywords
- renin, tissue kallikrein, connecting tubule, prorenin, renin activation, angiotensin I, collecting duct, gene expression regulation, kallikrein-kinin system
- MeSH terms
- Animals, Cricetinae, Immunohistochemistry, Kidney Tubules, Collecting, Male, Mice, Inbred C57BL, Renin, Staining and Labeling, CHO Cells, In Situ Hybridization, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Tissue Kallikreins, Mice
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