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Cyclic AMP stimulates renin gene transcription in juxtaglomerular cells

Jürgen Klar1, Peter Sandner, Markus W H Müller

  • 1Institut für Physiologie, Universität Regensburg, 93040 Regensburg, Germany. juergen.klar@vkl.uni-regensburg.de

Pflugers Archiv : European Journal of Physiology
|July 12, 2002
PubMed

Insights

Cyclic AMP (cAMP) activates renin gene expression in juxtaglomerular cells via protein kinase A and CRE-binding protein phosphorylation. This study clarifies the molecular pathway for cAMP-mediated renin regulation.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Physiology

Background:

  • The cyclic AMP (cAMP) signaling cascade is a primary activator of renin gene expression in renal juxtaglomerular (JG) cells.
  • The precise molecular mechanisms by which cAMP influences renin gene expression remain incompletely understood.

Purpose of the Study:

  • To elucidate the molecular pathways linking cAMP to renin gene expression in JG cells.
  • To investigate the role of protein kinase A and CRE-binding protein in cAMP-mediated renin regulation.

Main Methods:

  • Utilized the mouse JG cell line As4.1 for experiments.
  • Stimulated cells with forskolin and IBMX to activate adenylate cyclase.
  • Assessed renin mRNA levels, prorenin secretion, and renin promoter activity.
  • Employed protein kinase A inhibitor (H-89) and transcription inhibitor (actinomycin D).

Main Results:

  • Forskolin/IBMX treatment increased renin mRNA and prorenin secretion up to threefold.
  • Inhibition of protein kinase A significantly attenuated the forskolin/IBMX-induced stimulation.
  • Forskolin/IBMX enhanced the activity of a renin promoter fragment containing putative CRE-sites.
  • CRE-binding protein phosphorylation was observed upon forskolin/IBMX stimulation.

Conclusions:

  • cAMP stimulates renin gene expression in JG cells through the activation of protein kinase A.
  • Phosphorylation of the CRE-binding protein is a key downstream event in this pathway.
  • This study clarifies the molecular mechanism of cAMP-mediated renin regulation in JG cells.

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