Quantitative Proteomic analysis on Activated Hepatic Stellate Cells reversion Reveal STAT1 as a key regulator between Liver Fibrosis and recovery.
Understanding the changes of activated HSCs reversion is an essential step toward clarifying the potential roles of HSCs in the treatment of liver fibrosis. In this study, we chose adipocyte differentiation mixture to induce LX-2 cells for 2 days in vitro as reversion phase, comparing with normal cultured LX-2 cells as activation phase. Mass spectrometric-based SILAC technology was adopted to study differentially expressed proteome of LX-2 cells between reversion and activation. Compared with activated HSCs, 273 proteins showed significant differences in reverted HSCs. The main pathway of up-regulated proteins associated with reversion of HSCs mainly related to oxidation-reduction and lipid metabolism, while the top pathway of down-regulated proteins was found in regulated cytoskeleton formation. Changes in the expression levels of selected proteins were verified by Western blotting analysis, especially STAT1, FLNA, LASP1, and NAMPT proteins. The distinct roles of STAT1 were further analyzed between activated and reverted of HSCs, it was found that STAT1 could affect cell proliferation of HSCs and could be viewed as a key regulator in the reversion of HSCs. Thus, the proteomic analysis could accelerate our understanding of the mechanisms of HSC reversion on cessation of fibrogenic stimuli and provide new targets for antifibrotic liver therapy.
State Key Laboratory of Proteomics, National Center for Protein Sciences Beijing, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China.|School of Life Sciences, Tsinghua University, Beijing, 100084, P. R. China.|State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing, 100094, P. R. China.
Hongyu
H
Zhang
State Key Laboratory of Proteomics, National Center for Protein Sciences Beijing, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China.
Fangyan
F
Chen
State Key Laboratory of Proteomics, National Center for Protein Sciences Beijing, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China.
Xu
X
Fan
State Key Laboratory of Proteomics, National Center for Protein Sciences Beijing, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China.
Cong
C
Lin
State Key Laboratory of Proteomics, National Center for Protein Sciences Beijing, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China.
Yunwei
Y
Hao
State Key Laboratory of Proteomics, National Center for Protein Sciences Beijing, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China.
Handong
H
Wei
State Key Laboratory of Proteomics, National Center for Protein Sciences Beijing, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China.
Weiran
W
Lin
State Key Laboratory of Proteomics, National Center for Protein Sciences Beijing, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China.
Ying
Y
Jiang
State Key Laboratory of Proteomics, National Center for Protein Sciences Beijing, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China.
Fuchu
F
He
D000818:Animals; D015415:Biomarkers; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation; D019295:Computational Biology / Q000379:methods; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D020543:Proteome; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D050794:STAT1 Transcription Factor / Q000378:metabolism*
D015415:Biomarkers; D020543:Proteome; D050794:STAT1 Transcription Factor