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
,
2
;
Li BAN
;
Songlin TIAN
;
Qiulian ZHU
;
Guiping ZHANG
;
Yuan QIN
;
Li PAN
;
Ning HOU
Author Information
1. 广州医科大学药学院药理学教研室//广州医科大学分子靶标与临床药理学重点实验室,广东 广州 511436
2. 广州医科大学附属第五医院,广东 广州 510799
- 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:
[Objective]To explore how hyperthyroidism induces ventricular remodeling via activating β-catenin/FoxO1 in rat cardiomyocytes.[Methods]Hyperthyroidism-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 admin-istrated 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.Hyperthy-roidism-induced cardiomyocyte hypertrophy rat models were established by treatment of triiodothyronine(T3)into cul-tured 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.[Results]Following Wnt/β-catenin activation,β-catenin was found increased nuclear expression,to bind to the nuclear transcriptional factors and regulate the gene ex-pression.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.[Conclusions]β-catenin/FoxO1 is activated in hyperthy-roidism-induced myocardial hypertrophy and β-catenin/FoxO1 inhibition attenuates hyperthyroidism-induced cardiomyo-cyte hypertrophy.
