Curt D. Sigmund, Ph.D.

Professor and Head

Office Room #:2-454 BSB
Office Phone #:319-335-7946

Lab Room #:3171 MERF
Lab Phone #:319-335-8926

Lab Website:

Molecular mechanisms regulating transcription of the renin gene; Role of PPARγ in vascular function and hypertension

My laboratory has three primary interests: 1) investigating the regulation of genes involved in cardiovascular homeostasis using both cell culture and transgenic model systems, 2) modeling hypertensive disease using transgenic mice, and 3) examining the role of PPARγ in the regulation of vascular function. For the past 10 years we have been examining the regulation of the gene encoding a protein (renin) central to the regulation of blood pressure and water and electrolyte homeostasis. We identified a strong enhancer of transcription 2.6 kb upstream of the mouse renin gene and its homolog 12.0 kb upstream of the human renin gene. This enhancer is a complex regulatory element consisting of the binding sites for at least 10 different transcription factors including NF-Y, RARα, RXRα, CREM, CREB, Ear2, STAT3, VDR, USF-1 and USF-2. These transcription factors serve to both up-regulate and down-regulate renin expression in response to physiological cues.

Peroxisome proliferator activated receptors (PPAR’s) are ligand activated transcription factors which have a pleiotropic role in many physiological processes. PPARγ is the molecular target of the thiazolidinediones drugs which are used to treat patients with non-insulin dependent diabetes mellitus (NIDDM). PPARγ is expressed in vascular endothelium and smooth muscle and therefore is a potentially important factor in the regulation of vascular function and blood pressure. Moreover, patients carrying dominant negative mutations in PPARγ exhibit early onset type II diabetes and hypertension. We hypothesize that PPARγ plays an important role in the regulation of vascular function and blood pressure. We will test this hypothesis using transgenic and viral transfer technologies, in order to gain new insight into PPARγ’s physiological and pathophysiological role in the carotid artery and cerebral circulation. To test this hypothesis, we generated transgenic mice with expression of the wild-type and dominant negative mutants of PPARγ targeted specifically to vascular muscle and endothelial cells using cell-specific promoters.

PubMed link

Department/Program Affiliations:
Internal Medicine
Molecular Medicine
Molecular Physiology and Biophysics