Pflügers Archiv - European Journal of Physiology

, Volume 469, Issue 10, pp 1349–1357 | Cite as

The PPAR-gamma-binding sequence Pal3 is necessary for basal but dispensable for high-fat diet regulated human renin expression in the kidney

  • Peter Lachmann
  • Jenny Selbmann
  • Linda Hickmann
  • Bernd Hohenstein
  • Christian Hugo
  • Vladimir T. Todorov
Molecular and genomic physiology
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Part of the following topical collections:
  1. Molecular and genomic physiology

Abstract

We reported earlier that PPAR-gamma regulates renin transcription through a human-specific atypical binding sequence termed hRen-Pal3. Here we developed a mouse model to investigate the functional relevance of the hRen-Pal3 sequence in vivo since it might be responsible for the increased renin production in obesity and thus for the development of accompanying arterial hypertension. We used bacterial artificial chromosome construct and co-placement strategy to generate two transgenic mouse lines expressing the human renin gene from identical genomic locus without affecting the intrinsic mouse renin expression. One line carried a wild-type hRen-Pal3 in the transgene (Pal3wt strain) and the other a mutated non-functional Pal3 (Pal3mut strain). Human renin expression was correctly targeted to the renin-producing juxtaglomerular (JG) cells of kidney in both lines. However, Pal3mut mice had lower basal human renin expression. Since human renin does not recognize mouse angiotensinogen as substrate, the blood pressure was not different between the strains. Stimulation of renin production with the angiotensin-converting enzyme inhibitor enalapril equipotentially stimulated the human renin expression in Pal3wt and Pal3mut mice. High-fat diet for 10 weeks which is known to activate PPAR-gamma failed to increase human renin mRNA in kidneys of either strain. These findings showed that the human renin PPAR-gamma-binding sequence hRen-Pal3 is essential for basal renin expression but dispensable for the cell-specific and high-fat diet regulated renin expression in the kidney.

Keywords

Transgene co-placement Pal3 sequence PPAR-gamma Renin High-fat diet 
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Notes

Acknowledgements

This work was supported by Deutsche Forschungsgemeinschaft Grants SFB 699/B1, TO 679/1-1, TO 679/2-1 (to V.T.T.) and HU-600/6-1, HU-600/8-1 (to C.H.). The competent technical assistance of Anelia Todorova, Manuela Brandt, Kathleen Fischer, Anika Lüdemann, Andrea Wagner and Doreen Weigel is gratefully acknowledged.

Compliance with ethical standards

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

Supplementary material

424_2017_1994_MOESM1_ESM.docx (37 kb)
Supplementary Fig. S1 (DOCX 36 kb)
424_2017_1994_MOESM2_ESM.docx (142 kb)
Supplementary Fig. S2 (DOCX 142 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Peter Lachmann
    • 1
  • Jenny Selbmann
    • 1
  • Linda Hickmann
    • 1
  • Bernd Hohenstein
    • 1
  • Christian Hugo
    • 1
  • Vladimir T. Todorov
    • 1
  1. 1.Experimental Nephrology, Division of Nephrology, Department of Internal Medicine IIIUniversity Hospital Carl Gustav Carus, Technische Universität DresdenDresdenGermany

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