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Identification of bona fide alternative renin transcripts expressed along cortical tubules and potential roles in promoting insulin resistance in vivo without significant plasma renin activity elevation
- Source :
- Hypertension (Dallas, Tex. : 1979). 64(1)
- Publication Year :
- 2014
-
Abstract
- Renin belongs to a family of aspartyl proteases and is the rate-limiting enzyme in the synthesis of the potent vasoactive peptide angiotensin II. Processing of renal renin has been extensively investigated in juxtaglomerular granular cells, in which prorenin and active renin are present in secretory condensed granules. Previous studies demonstrated alternative renin transcription in rat adrenal glands. Different studies reported novel intracellular forms of renin deduced from novel 5′ variants derived from renin mRNA in both mice and humans. Comprehensive detailed studies in genetically engineered mice showed that both a secreted and an intracellular form of renin plays divergent mechanism regulating fluid intake and metabolism by the brain renin–angiotensin system; however, the presence, regulation, and functions of these renin isoforms in kidney and adrenal gland are not fully understood in mice. To investigate the characteristics of renin isoforms in mice, we performed a systematic inventory of renin transcripts of mice with and without a duplication of the renin gene alternatively from previous studies. We discovered a novel isoform of renin of the Ren2 gene, which conserved functionally important residues of the prosegment and incomplete isoforms of the Ren1C/D gene lacking a pre-pro segment. In situ hybridization assays revealed alternative renin isoforms expressed along cortical tubules. Newly generated transgenic mice with systemic overexpression of alternative renin transcript showed enhanced local angiotensin II generation without elevation of plasma renin activity and systemic insulin resistance in vivo, providing new pathophysiological insights into insulin resistance exaggerated by bona fide renin isoform.
- Subjects :
- Gene isoform
Genetically modified mouse
Kidney
medicine.medical_specialty
Adrenal gland
Mice, Transgenic
In situ hybridization
Biology
Plasma renin activity
Angiotensin II
Renin-Angiotensin System
Mice
medicine.anatomical_structure
Endocrinology
Kidney Tubules
Internal medicine
Renin–angiotensin system
Adrenal Glands
Renin
Internal Medicine
medicine
Animals
Insulin Resistance
Subjects
Details
- ISSN :
- 15244563
- Volume :
- 64
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Hypertension (Dallas, Tex. : 1979)
- Accession number :
- edsair.doi.dedup.....c3d955556f9abe5bb3257d9326824616