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Exogenous high-mobility group box 1 protein prevents postinfarction adverse myocardial remodeling through TGF-β/Smad signaling pathway

Authors

  • Yiyu He,

    1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China
    2. Cardiovascular Research Institute of Wuhan University, Wuhan 430060, P.R. China
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  • Xiaoya Zhou,

    1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China
    2. Cardiovascular Research Institute of Wuhan University, Wuhan 430060, P.R. China
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  • Xiaoxin Zheng,

    1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China
    2. Cardiovascular Research Institute of Wuhan University, Wuhan 430060, P.R. China
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  • Xuejun Jiang MD

    Corresponding author
    1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China
    2. Cardiovascular Research Institute of Wuhan University, Wuhan 430060, P.R. China
    • Division of Cardiology, Cardiovascular Research Institute of Wuhan University, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang, Wuhan 430060, P.R. China.
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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-β) 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-β 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-β1 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-β/Smad signaling pathway. J. Cell. Biochem. 114: 1634–1641, 2013. © 2013 Wiley Periodicals, Inc.

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