Desch, Michael and Harlander, Sabine and Neubauer, Bjoern and Gerl, Melanie and Germain, Stephane and Castrop, Hayo and Todorov, Vladimir T. (2011) cAMP target sequences enhCRE and CNRE sense low-salt intake to increase human renin gene expression in vivo. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 461 (5). pp. 567-577. ISSN 0031-6768,
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This study aimed to assess the role of cAMP target sequences enhancer cAMP response element (enhCRE) and cAMP and overlapping negative response element (CNRE) in the control of human renin gene (REN) in vivo. enhCRE and CNRE were silenced by mutations in a 12.2-kb human renin promoter fused to LacZ reporter gene. This construct was used to generate transgenic mice (RENMut-LacZ). The expression of the transgene was correctly targeted to the juxtaglomerular portions of renal afferent arterioles which express endogenous mouse renin. Therefore, enhCRE and CNRE do not seem to be relevant for the control of the cell-specific expression of the human renin gene. The beta-adrenoreceptor agonist isoproterenol (10 mg/kg/day, for 2 days) stimulated the endogenous renin, but not the LacZ mRNA expression. Treatment of RENMut-LacZ mice with the angiotensin converting enzyme inhibitor (enalapril 10 mg/kg/day, for 7 days) or their crossing to angiotensin receptor type 1a knockout mice led to increased renin and LacZ mRNA levels. Renin expression was upregulated by low-salt diet (0.03% NaCl, for 10 days) and downregulated by high-salt diet (4% NaCl, for 10 days). In contrast, low-salt diet did not influence, while high-salt diet inhibited the expression of LacZ. In summary, enhCRE and CNRE appear to be necessary for the transactivation of the human renin gene through beta-adrenoreceptors and by low-salt diet. Our data also suggest that different intracellular mechanisms mediate the effect of low- and high-salt intake on renin expression in vivo.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACTIVATED-RECEPTOR-GAMMA; AMP RESPONSE ELEMENT; BLOOD-PRESSURE; CALU-6 CELLS; JUXTAGLOMERULAR CELLS; REGULATORY ELEMENTS; PROXIMAL PROMOTER; BINDING PROTEIN; LXR-ALPHA; TRANSCRIPTION; cAMP; Cell culture; Gene expression; Renin; Transgenic mouse |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Jun 2020 07:12 |
| Last Modified: | 22 Jun 2020 07:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/20921 |
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