Role of PPARgamma in the regulation of renin gene expression: from molecule to organism

• Applicant: Professor Dr. Vladimir Todorov
• Subject Area: Nephrology
• Term: from 2012 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 210362562

This project aims to investigate the role of nuclear receptor PPARgamma in the transcriptional control of the renin gene. We have described that PPARgamma is involved in the regulation of renin expression and that the human renin gene has a unique PPARgamma binding sequence termed Pal3. The Pal3 motif mediates a stronger transactivation of the human renin gene in comparison with the mouse renin gene. Therefore the human renin Pal3 site will be further characterized in vitro by studying its transcription factor-binding features as well as the expression pattern of nuclear receptors in native and immortalized clonal renin-producing cells. Next, the role of the Pal3 sequence in the control of the human renin gene expression in vivo will be investigated. To this end, two humanized mouse lines with wild-type or mutated Pal3 will be generated by transgene co-placement. At last, the relevance of PPARgamma for the renin overproduction and the development of arterial hypertension during obesity will be elucidated. For this purpose, mice with PPARgamma deficiency in the reninproducing cells will be used as model. We expect from these experiments novel data regarding the intracellular machinery which controls renin expression. This knowledge is clinically relevant because it will contribute to the overall understanding of the renin-angiotensin-system and thus of the molecular mechanisms of arterial hypertension.

• DFG Programme: Research Grants