Journal article
Preservation of Intracellular Renin Expression Is Insufficient to Compensate for Genetic Loss of Secreted Renin
Hypertension, Vol.54(6), pp.1240-U34
12/01/2009
DOI: 10.1161/HYPERTENSIONAHA.109.138677
PMCID: PMC2783841
PMID: 19822797
Abstract
The primary product of the renin gene is preprorenin. A signal peptide sorts renin to the secretory pathway in juxtaglomerular cells where it is released into the circulation to initiate the renin-angiotensin system cascade. In the brain, transcription of renin occurs from an alternative promoter encoding an mRNA starting with a new first exon (exon 1b). Exon 1b initiating transcripts skip over the classical first exon (exon 1a) containing the initiation codon for preprorenin. Exon 1b transcripts are predicted to use a highly conserved initiation codon within exon 2, producing renin, which should remain intracellular, because it lacks the signal peptide. To evaluate the roles of secreted and intracellular renin, we took advantage of the organization of the renin locus to generate a secreted renin (sRen)-specific knockout, which preserves intracellular renin expression. Expression of sRen mRNA was ablated in the brain and kidney, whereas intracellular renin mRNA expression was preserved in fetal and adult brains. We noted a developmental shift from the expression of sRen mRNA in the fetal brain to intracellular renin mRNA in the adult brain. Homozygous sRen knockout mice exhibited very poor survival at weaning. The survivors exhibited renal lesions, low hematocrit, an inability to generate a concentrated urine, decreased arterial pressure, and impaired aortic contraction. These results suggest that preservation of intracellular renin expression in the brain is not sufficient to compensate for a loss of sRen, and sRen plays a pivotal role in renal development and function, survival, and the regulation of arterial pressure.
Details
- Title: Subtitle
- Preservation of Intracellular Renin Expression Is Insufficient to Compensate for Genetic Loss of Secreted Renin
- Creators
- Giulianna R. BorgesChristopher J. PelhamDi XuJustin L. GrobeBaoli Yang - University of IowaCurt D. Sigmund
- Resource Type
- Journal article
- Publication Details
- Hypertension, Vol.54(6), pp.1240-U34
- DOI
- 10.1161/HYPERTENSIONAHA.109.138677
- PMID
- 19822797
- PMCID
- PMC2783841
- NLM abbreviation
- Hypertension
- ISSN
- 0194-911X
- Copyright
- 2009 © American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. The American Heart Association is qualified 501(c)(3) tax-exempt organization.
- Language
- English
- Date published
- 12/01/2009
- Academic Unit
- Molecular Physiology and Biophysics; BioVentures Center; Obstetrics and Gynecology; Neuroscience and Pharmacology
- Record Identifier
- 9983557114402771
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