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Bone morphogenetic protein 4 mediates bile duct ligation induced liver fibrosis through activation of Smad1 and ERK1/2 in rat hepatic stellate cells

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单位: [1]Univ Manitoba, Fac Pharm, Winnipeg, MB R3T 2N2, Canada [2]China Japan Friendship Hosp, Inst Clin Med Sci, Dept Pharmacol, Beijing, Peoples R China [3]Univ Manitoba, Dept Internal Med, Fac Med, Sect Hepatol, Winnipeg, MB, Canada [*1]Univ Manitoba, Fac Pharm, 304-50 Sifton Rd, Winnipeg, MB R3T 2N2, Canada
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Bone morphogenetic proteins (BMPs) are the important cytokine involving in cell differentiation especially in bone morphogenesis. Hepatic stellate cells (HSCs) undergo a trans-differentiation during their activation after liver injury. Although it has been demonstrated that BMP2 and BMP4 significantly increased the abundance of smooth muscle alpha actin (alpha-SMA) in cultured HSCs, the expression of BMPs has not been examined during the activation of HSCs. In current study, we documented the expression of BMP4 in bile duct ligation (BDL) rats and HSCs in culture. We have found that the expression of BMP4 was significantly elevated in the liver of BDL rats. The increase in BMP4 protein showed two peaks during 6 weeks after BDL. The expression and phosphorylation of Smad1, ERK1/2 and p38 were also elevated after BDL. Moreover, there was a gradual elevation of BMP4 mRNA abundance during 24 days' in vitro Culture of HSCs. Furthermore, BMP4 stimulated phosphorylation of Smad1 and ERK1/2 in HSCs. In conclusion, BMP4 expression was significantly increased in the liver of BDL rats and HSCs in culture. These findings indicate that BMP4 may mediate HSC activation through activation of Smad1 and ERK1/2.

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出版当年[2005]版:
大类 | 2 区 生物
最新[2025]版:
大类 | 3 区 生物学
小类 | 3 区 细胞生物学 3 区 生理学
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出版当年[2004]版:
Q1 CELL BIOLOGY Q1 PHYSIOLOGY
最新[2023]版:
Q1 PHYSIOLOGY Q2 CELL BIOLOGY

影响因子: 最新[2023版] 最新五年平均[2021-2025] 出版当年[2004版] 出版当年五年平均[2000-2004] 出版前一年[2003版] 出版后一年[2005版]

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通讯机构: [*1]Univ Manitoba, Fac Pharm, 304-50 Sifton Rd, Winnipeg, MB R3T 2N2, Canada
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