Abstract |
Maintaining a healthy, anti-hypertrophic state in the heart prevents progression to cardiac failure. In humans, angiotensin II (AngII) indirectly and directly stimulates hypertrophy and progression, while estrogens acting through estrogen receptor beta (ERβ) inhibit these AngII actions. The KLF15 transcription factor has been purported to provide anti-hypertrophic action. In cultured neonatal rat cardiomyocytes, we found AngII inhibited KLF1 expression and nuclear localization, substantially prevented by estradiol (E2) or β-LGND2 (β-LGND2), an ERβ agonist. AngII stimulation of transforming growth factor beta expression in the myocytes activated p38α kinase via TAK1 kinase, inhibiting KLF15 expression. All was comparably reduced by E2 or β-LGND2. Knockdown of KLF15 in the myocytes induced myocyte hypertrophy and limited the anti-hypertrophic actions of E2 and β-LGND2. Key aspects were confirmed in an in-vivo model of cardiac hypertrophy. Our findings define additional anti-hypertrophic effects of ERβ supporting testing specific receptor agonists in humans to prevent progression of cardiac disease.
|
Authors | Neil Hoa, Lisheng Ge, Kenneth S Korach, Ellis R Levin |
Journal | Molecular and cellular endocrinology
(Mol Cell Endocrinol)
Vol. 470
Pg. 240-250
(07 15 2018)
ISSN: 1872-8057 [Electronic] Ireland |
PMID | 29127073
(Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
|
Copyright | Published by Elsevier B.V. |
Chemical References |
- Estrogen Receptor beta
- Klf15 protein, rat
- Kruppel-Like Transcription Factors
- Transforming Growth Factor beta
- Angiotensin II
- p38 Mitogen-Activated Protein Kinases
- MAP Kinase Kinase Kinases
- MAP kinase kinase kinase 7
|
Topics |
- Angiotensin II
(pharmacology)
- Animals
- Animals, Newborn
- Cardiomegaly
(prevention & control)
- Estrogen Receptor beta
(metabolism)
- Female
- Gene Expression Regulation
(drug effects)
- Kruppel-Like Transcription Factors
(metabolism)
- MAP Kinase Kinase Kinases
(metabolism)
- Male
- Models, Biological
- Myocytes, Cardiac
(metabolism, pathology)
- Rats
- Signal Transduction
- Transforming Growth Factor beta
(pharmacology)
- p38 Mitogen-Activated Protein Kinases
(metabolism)
|