Aldosterone-induced EGFR expression: interaction between the human mineralocorticoid receptor and the human EGFR promoter.

  title={Aldosterone-induced EGFR expression: interaction between the human mineralocorticoid receptor and the human EGFR promoter.},
  author={Claudia Grossmann and Alexander W. Krug and Ruth Freudinger and Sigrid Mildenberger and Katharina Voelker and Michael Gekle},
  journal={American journal of physiology. Endocrinology and metabolism},
  volume={292 6},
  • C. GrossmannA. Krug M. Gekle
  • Published 1 June 2007
  • Biology, Medicine
  • American journal of physiology. Endocrinology and metabolism
Aldosterone plays a key role in cardiovascular and renal injury. The underlying mechanisms are not completely understood. Because the epidermal growth factor receptor (EGFR) is involved in the development of fibrosis and vascular dysfunction, upregulation of EGFR expression by aldosterone-bound mineralocorticoid receptor (MR) is an attractive hypothesis. We investigated the effect of aldosterone on EGFR expression in the aorta of adrenalectomized rats and in human aorta smooth muscle cells… 

Figures and Tables from this paper

The mineralocorticoid receptor leads to increased expression of EGFR and T-type calcium channels that support HL-1 cell hypertrophy

The MR regulates EGFR and CACNA1H expression, which has an effect on HL-1 cell diameter, and the extent of this regulation seems to depend on the SNP-216 (G/T) genotype, which suggests that the EGFR may be an intermediate for MR-mediated cardiovascular changes and that SNP analysis can help identify subgroups of patients that will benefit most from MR antagonists.

The Epidermal Growth Factor Receptor Is Involved in Angiotensin II But Not Aldosterone/Salt-Induced Cardiac Remodelling

The findings confirm the role of EGFR in AngII mediated cardiac hypertrophy, and highlight that EGFR is not involved in vivo in the damaging effects of aldosterone on cardiac function and remodelling.

Non-classical actions of the mineralocorticoid receptor: Misuse of EGF receptors?

Role of epidermal growth factor receptor in the pathogenesis and treatment of arterial hypertension

Data suggest that inhibiting EGFR could be a novel therapeutic strategy for the treatment of hypertension, and some of currently used hypotensive medications, in particular inhibitors of the renin-angiotensin-aldosterone system, modulate EGFR signaling.

Aldosterone Stimulates the Cardiac Na+/H+ Exchanger via Transactivation of the Epidermal Growth Factor Receptor

The results call attention to the consideration of the EGFR as a new potential therapeutic target of the cardiovascular pathologies involving the participation of aldosterone.

Mineralocorticoid receptor interaction with SP1 generates a new response element for pathophysiologically relevant gene expression

Overall, a novel principle of MR-specific gene expression is explored that applies to the pathophysiologically relevant expression of the EGFR and potentially also to other genes.

Moderate inappropriately high aldosterone/NaCl constellation in mice: cardiovascular effects and the role of cardiovascular epidermal growth factor receptor

The data show that cardiac tissue of male but not of female mice is sensitive to mild aldosterone/NaCl treatment, and EGFR knockout induces stronger cardiac disturbances in male as compared to female animals, whereas beneficial effects of ald testosterone seem to be independent of EGFR.

Aldosterone Stimulates Epidermal Growth Factor Receptor Expression*

It is shown that aldosterone stimulates EGFR expression in renal tissue of adrenalectomized rats and in human renal primary cell cultures, suggesting that EGFR is an a Aldosterone-induced protein and is involved in the manifold (patho)biological actions of ald testosterone.

Human mineralocorticoid receptor expression renders cells responsive for nongenotropic aldosterone actions.

It is concluded that some nongenotropic effects of aldosterone are MR dependent and others are MR independent (e.g. Ca2+), indicating a higher degree of complexity of rapid ald testosterone signaling.

Antisense to Epidermal Growth Factor Receptor Prevents the Development of Left Ventricular Hypertrophy

Results suggests that EGFR-mediated ERK activation is critically important for LVH in young SHR, and may be related to the high levels of EGFR and phosphorylated ERK in youngSHR, suggesting a critical role of the EG FR-activated ERK pathway in cardiovascular development but not in the maintenance of established LVh in adult SHR.

Altered collagen homeostasis in human aortic smooth muscle cells (HAoSMCs) induced by aldosterone

It is concluded that aldosterone sensitizes HAoSMC for H2O2-induced increase of collagen abundance at least in part by enhanced EGFR expression.

Angiotensin II–Induced Cardiac Hypertrophy and Hypertension Are Attenuated by Epidermal Growth Factor Receptor Antisense

EGFR plays a critical role in the LVH induced by Ang II and requires EGFR to mediate ERK activation in VSMCs and the heart.

Angiotensin II and EGF receptor cross-talk in chronic kidney diseases: a new therapeutic approach

It is shown that mice overexpressing a dominant negative isoform of epidermal growth factor receptor (EGFR) were protected from renal lesions during chronic AngII infusion, indicating a crucial role for AngII-dependent EGFR transactivation in renal deterioration and identifying in TACE inhibitors a new therapeutic strategy for preventing progression of chronic renal diseases.

Human Epidermal Growth Factor Receptor-1 Expression Renders Chinese Hamster Ovary Cells Sensitive to Alternative Aldosterone Signaling*

The hypothesis that human EGFR-1 can confer alternative aldosterone responsiveness with respect to ERK1/2 phosphorylation to Chinese hamster ovary cells, which do not express EGFR, is tested and data show that ald testosterone uses the EGF-EGFR-MEK1-2-ERK 1/2 signaling cascade to elicit its alternative effects.

Aldosterone Potentiates Angiotensin II–Induced Signaling in Vascular Smooth Muscle Cells

Oxygen radicals, the MR, and the EGFR play a role in early signaling induced by Ang II and Ald in VSMCs and may help explain the effects of MR blockade on Ang II–induced end-organ damage in vivo.

Epidermal growth factor receptor transactivation mediates the tonic and fibrogenic effects of endothelin in the aortic wall of transgenic mice

  • M. FlamantP. Tharaux J. Dussaule
  • Biology, Chemistry
    FASEB journal : official publication of the Federation of American Societies for Experimental Biology
  • 2003
The results provide the first evidence that the EGF receptor mediates at least two of the major actions of endothelin in the vascular tissue: contractility and fibrogenesis.

Early nongenomic events in aldosterone action in renal collecting duct cells: PKCalpha activation, mineralocorticoid receptor phosphorylation, and cross-talk with the genomic response.

Cross-talk between the nongenomic and genomic responses to aldosterone in renal cells is suggested and it is suggested that the ald testosterone-MR mediated increase in mRNA/protein synthesis and ion transport depends, at least in part, upon PKCalpha activation.