The Role Played by Transcription Factor E3 in Modulating Cardiac Hypertrophy
Autor: | Dan Gilon, Ehud Razin, Roger Foo, Sagi Tshori, Ilya Savchenko, Yoav Smith, Eliahu Golomb, Ran Eliaz, Ahmed Rishiq, Omedul Islam |
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Rok vydání: | 2021 |
Předmět: |
MAPK/ERK pathway
medicine.medical_specialty Cellular adaptation Down-Regulation Cardiomegaly Histones Internal medicine Medicine Animals Humans Phosphorylation Extracellular Signal-Regulated MAP Kinases Cardioprotection Mice Knockout Gene knockdown Ejection fraction Myosin Heavy Chains business.industry Kinase Basic Helix-Loop-Helix Leucine Zipper Transcription Factors General Medicine Disease Models Animal Endocrinology Knockout mouse Hypertension MYH7 Cardiology and Cardiovascular Medicine business |
Zdroj: | International heart journal. 62(6) |
ISSN: | 1349-3299 |
Popis: | Transcription factor E3 (TFE3), which is a key regulator of cellular adaptation, is expressed in most tissues, including the heart, and is reportedly overexpressed during cardiac hypertrophy. In this study, TFE3's role in cardiac hypertrophy was investigated. To understand TFE3's physiological importance in cardiac hypertrophy, pressure-overload cardiac hypertrophy was induced through transverse aortic constriction (TAC) in both wild-type (WT) and TFE3 knockout mice (TFE3-/-). Eleven weeks after TAC induction, cardiac hypertrophy was observed in both WT and TFE3-/- mice. However, significant reductions in ejection fraction and fractional shortening were observed in WT mice compared to TFE3-/- mice. To understand the mechanism, we found that myosin heavy chain (Myh7), which increases during hemodynamic overload, was lower in TFE3-/- TAC mice than in WT TAC mice, whereas extracellular signal-regulated protein kinases (ERK) phosphorylation, which confers cardioprotection, was lower in the left ventricles of WT mice than in TFE3-/- mice. We also found high expressions of TFE3, histone, and MYH7 and low expression of pERK in the normal human heart compared to the hypertensive heart. In the H9c2 cell line, we found that ERK inhibition caused TFE3 nuclear localization. In addition, we found that MYH7 was associated with TFE3, and during TFE3 knockdown, MYH7 and histone were downregulated. Therefore, we showed that TFE3 expression was increased in the mouse model of cardiac hypertrophy and tissues from human hypertensive hearts, whereas pERK was decreased reversibly, which suggested that TFE3 is involved in cardiac hypertrophy through TFE3-histone-MYH7-pERK signaling. |
Databáze: | OpenAIRE |
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