期刊
ASIAN PACIFIC JOURNAL OF CANCER PREVENTION
卷 15, 期 2, 页码 605-610出版社
ASIAN PACIFIC ORGANIZATION CANCER PREVENTION
DOI: 10.7314/APJCP.2014.15.2.605
关键词
Serum ferritin; hepatic stellate cells; liver fibrosis; Grp78; endoplasmic reticulum stress
类别
资金
- [99TMU-TMUH-02-2]
- [NSC101-2320-B-038-033]
- [102TMU-TMUH-16]
Chronic liver diseases, including cancer, are characterized by inflammation and elevated serum ferritin (SF). However, the causal-relationship remains unclear. This study used primary rat hepatic stellate cells (HSC) as a model to investigate effects of physiological SF concentrations (10, 100 and 1000 pM) because HSCs play a central role in the development and progression of liver fibrosis. Physiological concentrations of SF, either horse SF or human serum, induced pro-inflammatory cytokine IL1 beta, IL6 and TNF alpha secretion in rat activated HSCs (all p<0.05). By contrast, treatment did not alter activation marker alpha SMA expression. The presence of SF markedly enhanced expression of Grp78 mRNA (p<0.01). Furthermore, transient knock down of Grp78 by endotoxin EGF-SubA abolished SF-induced IL1 beta and TNF alpha secretion in activated HSCs (all p<0.05). In conclusion, our results showed that at physiological concentrations SF functions as a pro-inflammatory mediator in primary rat HSCs. We also provide a molecular basis for the action of SF and identified Grp78-associated ER stress pathways as a novel potential therapeutic target for resolution of fibrosis and possible prevention of liver cancer.
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