Exogenous high-mobility group box 1 protein prevents postinfarction adverse myocardial remodeling through TGF-ß/Smad signaling pathway.
J Cell Biochem
; 114(7): 1634-41, 2013 Jul.
Article
em En
| MEDLINE
| ID: mdl-23355476
ABSTRACT
High-mobility group box 1 (HMGB1) has been reported to attenuate ventricular remodeling, but its mechanism remains mostly unresolved. Transforming growth factor-beta (TGF-ß) is a crucial mediator in the pathogenesis of post-infarction remodeling. Our study focused on the effects of HMGB1 on ventricular remodeling, and explored whether or not these effects were depended upon the TGF-ß signaling pathway. Rats underwent coronary artery ligation. An intramyocardium injection of phosphate buffered saline (PBS) with or without HMGB1 was administered 3 weeks after myocardial infarction (MI). At 4 weeks after the treatment, HMGB1 significantly increased the left ventricular ejection fraction (LVEF) (P < 0.05), decreased the left ventricular end diastolic dimension (LVEDD; P < 0.05), left ventricular end systolic dimension (LVESD) (P < 0.05) and the infarct size (P < 0.05) compared with control group. The expressions of collagen I, collagen III, and tissue inhibitor of metalloproteinase 2 (TIMP2) were also decreased, while the matrix metalloproteinases 2 (MMP2) and MMP9 expressions were upregulated by HMGB1 injection (P < 0.05) compared with control group. No effect on TIMP3 was observed. Furthermore, TGF-ß1 and phosphor-Smad2 (p-Smad2) were significantly suppressed and Smad7 was increased in HMGB1-treated group (P < 0.05) compared with control group, no effects on p-Smad3 and p-p38 were observed. HMGB1 also upregulated Smad 7 expression and decreased the level of collagen I on cardiac fibroblasts (P < 0.05). Silencing of Smad7 gene by small interfering RNA abolished the fibrogenic effects of HMGB1 on cardiac fibroblasts (P < 0.05). These finding suggested that HMGB1 injection modulated ventricular remodeling may function through the possible inhibition of TGF-ß/Smad signaling pathway.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Transformador beta
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Remodelação Ventricular
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Proteína HMGB1
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Proteína Smad2
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Infarto do Miocárdio
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article