期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 463, 期 3, 页码 255-261出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2015.05.040
关键词
Hepatic stellate cells; RACK1; eIF4E; Liver fibrosis
资金
- State Key Project Specialized for Infectious Diseases of China [2012ZX10002-008]
- National Basic Research Program of China (973 Program) [2012CB822104]
- National Natural Science Fund [31370808, 81302259, 31100977]
- Specialized Research Fund for the Doctoral Program of Higher Education [20130071120044]
- China Postdoctoral Science Foundation [2014M551321]
Activation of quiescent hepatic stellate cells (HSCs) is the central event of liver fibrosis. The translational machinery is an optimized molecular network that affects cellular homoeostasis and diseases, whereas the role of protein translation in HSCs activation and liver fibrosis is little defined. Our previous report suggests that up-regulation of receptor for activated C-kinase 1(RACK1) in HSCs is critical for liver fibrogenesis. In this study, we found that RACK1 promoted macrophage conditioned medium (MCM)induced assembly of eIF4F and phosphorylation of eIF4E in primary HSCs. RACK1 enhanced the translation and expression of pro-fibrogenic factors collagen 1 alpha 1, snail and cyclin El induced by MCM. Administration of PP242 or knock-down of elF4E suppressed RACK1-stimulated collagen 1 alpha 1 production, proliferation and migration in primary HSCs. In addition, depletion of eIF4E attenuated thioacetamide (TAA)-induced liver fibrosis in vivo. Our data suggest that RACK1-mediated stimulation of cap-dependent translation plays crucial roles in HSCs activation and liver fibrogenesis, and targeting translation initiation could be a promising strategy for the treatment of liver fibrosis. (C) 2015 Elsevier Inc. All rights reserved.
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