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cAMP target sequences enhCRE and CNRE sense low-salt intake to increase human renin gene expression in vivo

  • Signaling and Cell Physiology
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Abstract

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 β-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 β-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.

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Acknowledgements

This study was supported by Deutsche Forschungsgemeinschaft grant SFB 699/B1 to V.T.T. We gratefully acknowledge the excellent technical assistance of Dr. Anelia Todorova and Sandra Mayer.

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Author notes

  1. Vladimir T. Todorov

    Present address: Laboratory for Experimental Nephrology, Department of Nephrology, University Clinic Carl Gustav Carus, Dresden University of Technology, D-01307, Dresden, Germany

Authors and Affiliations

  1. Institute of Physiology, University of Regensburg, 93040, Regensburg, Germany

    Michael Desch, Sabine Harlander, Björn Neubauer, Melanie Gerl, Hayo Castrop & Vladimir T. Todorov

  2. Experimental Medicine Unit, INSERM U833—College de France, Paris, France

    Stephane Germain

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  1. Michael Desch
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  2. Sabine Harlander
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Correspondence to Vladimir T. Todorov.

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Desch, M., Harlander, S., Neubauer, B. et al. cAMP target sequences enhCRE and CNRE sense low-salt intake to increase human renin gene expression in vivo. Pflugers Arch - Eur J Physiol 461, 567–577 (2011). https://doi.org/10.1007/s00424-011-0956-z

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  • DOI: https://doi.org/10.1007/s00424-011-0956-z

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