共 28 条
Osteopontin promotes collagen I synthesis in hepatic stellate cells by miRNA-129-5p inhibition
被引:54
作者:

Chen, Yinghua
论文数: 0 引用数: 0
h-index: 0
机构:
Sun Yat Sen Univ, Affiliated Ed Hosp 1, Organ Transplantat Ctr, Guangzhou 510080, Guangdong, Peoples R China Guangdong Pharmaceut Univ, Guangzhou 510006, Guangdong, Peoples R China

Ou, Yitao
论文数: 0 引用数: 0
h-index: 0
机构:
Guangdong Pharmaceut Univ, Guangzhou 510006, Guangdong, Peoples R China
Guangzhou Med Univ, Guangdong Prov Key Lab Mol Target & Clin Pharmaco, Sch Pharmaceut Sci, Guangzhou 511436, Guangdong, Peoples R China Guangdong Pharmaceut Univ, Guangzhou 510006, Guangdong, Peoples R China

Dong, Jiale
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h-index: 0
机构:
Guangdong Pharmaceut Univ, Guangzhou 510006, Guangdong, Peoples R China Guangdong Pharmaceut Univ, Guangzhou 510006, Guangdong, Peoples R China

Yang, Guizhi
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机构:
Guangdong Pharmaceut Univ, Guangzhou 510006, Guangdong, Peoples R China Guangdong Pharmaceut Univ, Guangzhou 510006, Guangdong, Peoples R China

Zeng, Zhi
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h-index: 0
机构:
Guangdong Pharmaceut Univ, Guangzhou 510006, Guangdong, Peoples R China Guangdong Pharmaceut Univ, Guangzhou 510006, Guangdong, Peoples R China

Liu, Ying
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h-index: 0
机构:
Guangdong Pharmaceut Univ, Guangzhou 510006, Guangdong, Peoples R China Guangdong Pharmaceut Univ, Guangzhou 510006, Guangdong, Peoples R China

Liu, Bing
论文数: 0 引用数: 0
h-index: 0
机构:
Guangdong Pharmaceut Univ, Guangzhou 510006, Guangdong, Peoples R China Guangdong Pharmaceut Univ, Guangzhou 510006, Guangdong, Peoples R China

Li, Weidong
论文数: 0 引用数: 0
h-index: 0
机构:
Guangdong Pharmaceut Univ, Guangzhou 510006, Guangdong, Peoples R China Guangdong Pharmaceut Univ, Guangzhou 510006, Guangdong, Peoples R China

He, Xiaoshun
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h-index: 0
机构:
Sun Yat Sen Univ, Affiliated Ed Hosp 1, Organ Transplantat Ctr, Guangzhou 510080, Guangdong, Peoples R China Guangdong Pharmaceut Univ, Guangzhou 510006, Guangdong, Peoples R China

Lan, Tian
论文数: 0 引用数: 0
h-index: 0
机构:
Guangdong Pharmaceut Univ, Guangzhou 510006, Guangdong, Peoples R China Guangdong Pharmaceut Univ, Guangzhou 510006, Guangdong, Peoples R China
机构:
[1] Guangdong Pharmaceut Univ, Guangzhou 510006, Guangdong, Peoples R China
[2] Sun Yat Sen Univ, Affiliated Ed Hosp 1, Organ Transplantat Ctr, Guangzhou 510080, Guangdong, Peoples R China
[3] Guangzhou Med Univ, Guangdong Prov Key Lab Mol Target & Clin Pharmaco, Sch Pharmaceut Sci, Guangzhou 511436, Guangdong, Peoples R China
基金:
中国国家自然科学基金;
关键词:
Osteopontin;
Collagen I;
Liver fibrosis;
Hepatic stellate cells;
miR-129-5p;
LIVER FIBROSIS;
CANCER;
PROGRESSION;
ACTIVATION;
MICRORNAS;
CONTRIBUTES;
EXPRESSION;
TARGET;
MODEL;
D O I:
10.1016/j.yexcr.2017.11.035
中图分类号:
R73 [肿瘤学];
学科分类号:
100214 ;
摘要:
Activation of hepatic stellate cells (HSCs) is an essential event in the initiation and progression of liver fibrosis. HSCs are believed to be the major source of collagen-producing myofibroblasts in fibrotic livers. A key feature in the pathogenesis of liver fibrosis is fibrillar Collagen I (Col 1) deposition. Osteopontin (OPN), an extracellular matrix (ECM) cytokine expressed in HSCs, could drive fibrogenesis by modulating the HSC pro-fibrogenic phenotype and Col 1 expression. Here, we aimed to investigate the molecular mechanism of OPN regulating the activation of HSCs. Our results showed that hepatic expression of OPN was increased in patients with liver fibrosis. In addition, hepatic OPN was positively correlated with Col 1 and alpha-SMA. Recombinant OPN (rOPN) upregulated Col 1 and alpha-SMA expression in LX-2 cells. However, OPN knockdown downregulated Col 1 expression. The 3'-UTR of the collagen 1 (Col 1) was identified to bind miR-129-5p. Transfection of miR-129-5p mimic in HSC resulted in a marked reduction of Col 1 expression. Conversely, a decrease in miR-129-5p in HSCs transfected by anti-sense miR-129-5p (AS-miR-129-5p) caused Col 1 upregulation. Furthermore, luciferase reporter assay showed that miR-129-5p directly target the 3'-UTR of Coll alpha 1 mRNA via repressing its post-transcriptional activities. Finally, miR-129-5p level was decreased in fibrotic liver of human, and reduced by rOPN treatment. In contrast, miR-129-5p was induced in HSCs transfected by OPN siRNA. These data suggested that OPN induces Col 1 expression via suppression of miR-129-5p in HSCs.
引用
收藏
页码:343 / 348
页数:6
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JOURNAL OF MOLECULAR CELL BIOLOGY,
2016, 8 (05)
:400-410

Han, Han
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Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China

Li, Wenjuan
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Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China

Shen, Hongxing
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Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China

Zhang, Jinxiang
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Wuhan Union Hosp, Dept Surg, Wuhan 430022, Peoples R China Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China

Zhu, Yahui
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Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China

Li, Youjun
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Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China Wuhan Univ, Med Res Inst, Coll Life Sci, Wuhan 430072, Peoples R China