Ghrelin attenuates plasminogen activator inhibitor-1 production induced by tumor necrosis factor-α in HepG2 cells via NF-κB pathway

Authors

  • Liying Ding,

    1. Department of Endocrinology, First Hospital of China Medical University, ShenYang 110001, China
    2. Department of Endocrinology, First Hospital of Liaoning Medical College, JinZou 121000, China
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  • Guoliang Liu,

    Corresponding author
    1. Department of Endocrinology, First Hospital of China Medical University, ShenYang 110001, China
      Corresponding author. Department of Endocrinology, First Hospital of China Medical University, 155, Nanjing North Street Heping District Shenyang, 110001, China. Fax: +86 24 2386 3781. liyingding1973@hotmail.com
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  • Wenshi Guo,

    1. Department of Endocrinology, First Hospital of Liaoning Medical College, JinZou 121000, China
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  • Hong Zhao,

    1. Department of Endocrinology, First Hospital of China Medical University, ShenYang 110001, China
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  • Zhihong Zong

    1. Department of Biochemistry, China Medical University, ShenYang 110001, China
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Corresponding author. Department of Endocrinology, First Hospital of China Medical University, 155, Nanjing North Street Heping District Shenyang, 110001, China. Fax: +86 24 2386 3781. liyingding1973@hotmail.com

Abstract

Plasminogen activator inhibitor type 1 (PAI-1), produced partly from liver is a risk factor for macrovascular and microvascular complications of diabetes. Ghrelin, a recently described orexigenic peptide hormone, attenuates PAI-1 induced by TNF-α in the human hepatoma cell line (HepG2). Exposure to TNF-α (1 ng/ml) for 24 h caused a significant increase in PAI-1 mRNA expression and protein secretion, as evaluated by RT-PCR and ELISA, but pretreatment with ghrelin (1–100 ng/ml) inhibited both basal and TNF-α-induced PAI-1 release in a dose and time-dependent manner in HepG2. PDTC, selective NF-κB inhibitor, had no additive inhibitory effects with ghrelin. The results indicate that ghrelin inhibits both basal and TNF-α-induced PAI-1 production via NF-κB pathway in HepG2 cells, and suggest that the peptide plays a therapeutic role in atherosclerosis, especially in obese patients with insulin resistance, in whom ghrelin levels were reduced.

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