Hyperthyroidism Induces Ventricular Remodeling via Activating β-catenin/FoxO1 in Rat Cardiomyocytes
10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.20240515.003
- VernacularTitle:甲状腺功能亢进激活心肌细胞β-catenin/FoxO1诱导大鼠心室重构的作用
- Author:
Xun YUAN
1
;
Li BAN
2
;
Songlin TIAN
1
;
Qiulian ZHU
1
;
Guiping ZHANG
1
;
Yuan QIN
1
;
Li PAN
3
;
Ning HOU
1
Author Information
1. Department of Pharmacology， School of Pharmaceutical Sciences， Guangzhou Medical University // Laboratory of Molecular Target & Clinical Pharmacology， School of Pharmaceutical Sciences， Guangzhou Medical University， Guangzhou 511436， China
2. The Fifth Affiliated Hospital of Guangzhou Medical University， Guangzhou 510799， China
3. Department of Physiology， Guangzhou Health Science College， Guangzhou 510450， China
- Publication Type:Journal Article
- Keywords:
hyperthyroidism;
myocardial hypertrophy;
β-catenin;
FoxO1;
cardiomyocyte hypertrophy;
MSAB;
thyroid hormone
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2024;45(3):393-411
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore how hyperthyroidism induces ventricular remodeling via activating β-catenin/FoxO1 in rat cardiomyocytes. MethodsHyperthyroidism-induced ventricular remodeling rat models were established by intraperitoneal injection of levothyroxine （T4） at 0.1 mg/kg for 30 days. β-catenin inhibitor MSAB （14 mg/kg） was administrated for 30 days. We used western blot to detect the expression of myocardial hypertrophy marker ANP， β-catenin and FoxO1； immunofluorescence to examine the expression and intracellular distribution of β-catenin and FoxO1. Hyperthyroidism-induced cardiomyocyte hypertrophy rat models were established by treatment of triiodothyronine （T3） into cultured primary neonatal rat cardiomyocytes for 24 hours. β-catenin siRNA （30 nmol/L） was used to down-regulate β-catenin expression in cardiomyocytes. Western blot and immunofluorescence were used to analyze the effects of β-catenin inhibition on the hyperthyroidism-induced cardiomyocyte hypertrophy. ResultsFollowing Wnt/β-catenin activation， β-catenin was found increased nuclear expression， to bind to the nuclear transcriptional factors and regulate the gene expression. β-catenin nuclear expression was significantly increased in the hyperthyroidism-induced ventricular remodeling rats， but no change was found in the expression of typical transcriptional factor TCF7l2. Our results revealed that inhibiting β-catenin by MSAB attenuated the hyperthyroidism-induced rat ventricular remodeling. Further analysis indicated that β-catenin/FoxO1 expression was significantly increased in hyperthyroidism-induced myocardial hypertrophy which could be attenuated by suppressing β-catenin/FoxO1 in cardiomyocytes. Conclusionsβ-catenin/FoxO1 is activated in hyperthyroidism-induced myocardial hypertrophy and β-catenin/FoxO1 inhibition attenuates hyperthyroidism-induced cardiomyocyte hypertrophy.
