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Proteomic Profiling of Human Hepatic Stellate Cell Line LX2 Responses to Irradiation and TGF-β1.

Publication ,  Journal Article
Yuan, B; Chen, Y; Wu, Z; Zhang, L; Zhuang, Y; Zhao, X; Niu, H; Cheng, JC-H; Zeng, Z
Published in: Journal of proteome research
January 2019

Hepatic stellate cells (HSCs) are the main target of radiation damage and primarily contribute to the development of radiation-induced liver fibrosis. However, the molecular events underlying the radiation-induced activation of HSCs are not fully elucidated. In the present study, human HSC line LX2 was treated with X-ray irradiation and/or TGF-β1, and profibrogenic molecules were evaluated. The iTRAQ LC-MS/MS technology was performed to identify global protein expression profiles in LX2 following exposure to different stimuli. Irradiation or TGF-β1 alone increased expression of α-SMA, collagen 1, CTGF, PAI-1, and fibronectin. Irradiation and TGF-β1 cooperatively induced expression of these profibrotic markers. In total, 102, 137, 155 dysregulated proteins were identified in LX2 cell samples affected by irradiation, TGF-β1, or cotreatment, respectively. Bioinformatic analyses showed that the three differentially expressed protein sets were commonly associated with cell cycle and protein processing in endoplasmic reticulum. The expression of a set of proteins was properly validated: CDC20, PRC1, KIF20A, CCNB1, SHCBP, TACC3 were upregulated upon irradiation or irradiation and TGF-β1 costimulation, whereas SPARC and THBS1 were elevated by TGF-β1 or TGF-β1 plus irradiation treatment. Furthermore, CDC20 inhibition suppressed expression of profibrotic markers in irradiated and TGF-β1-stimulated LX2 cells. Detailed data on potential molecular mechanisms causing the radiation-induced HSC activation presented here would be instrumental in developing radiotherapy strategies that minimize radiation-induced liver fibrosis.

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Published In

Journal of proteome research

DOI

EISSN

1535-3907

ISSN

1535-3893

Publication Date

January 2019

Volume

18

Issue

1

Start / End Page

508 / 521

Related Subject Headings

  • X-Rays
  • Transforming Growth Factor beta1
  • Tandem Mass Spectrometry
  • Proteomics
  • Proteome
  • Liver Cirrhosis
  • Humans
  • Hepatic Stellate Cells
  • Gene Expression Regulation
  • Computational Biology
 

Citation

APA
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ICMJE
MLA
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Yuan, B., Chen, Y., Wu, Z., Zhang, L., Zhuang, Y., Zhao, X., … Zeng, Z. (2019). Proteomic Profiling of Human Hepatic Stellate Cell Line LX2 Responses to Irradiation and TGF-β1. Journal of Proteome Research, 18(1), 508–521. https://doi.org/10.1021/acs.jproteome.8b00814
Yuan, Baoying, Yuhan Chen, Zhifeng Wu, Li Zhang, Yuan Zhuang, Xiaomei Zhao, Hao Niu, Jason Chia-Hsien Cheng, and Zhaochong Zeng. “Proteomic Profiling of Human Hepatic Stellate Cell Line LX2 Responses to Irradiation and TGF-β1.Journal of Proteome Research 18, no. 1 (January 2019): 508–21. https://doi.org/10.1021/acs.jproteome.8b00814.
Yuan B, Chen Y, Wu Z, Zhang L, Zhuang Y, Zhao X, et al. Proteomic Profiling of Human Hepatic Stellate Cell Line LX2 Responses to Irradiation and TGF-β1. Journal of proteome research. 2019 Jan;18(1):508–21.
Yuan, Baoying, et al. “Proteomic Profiling of Human Hepatic Stellate Cell Line LX2 Responses to Irradiation and TGF-β1.Journal of Proteome Research, vol. 18, no. 1, Jan. 2019, pp. 508–21. Epmc, doi:10.1021/acs.jproteome.8b00814.
Yuan B, Chen Y, Wu Z, Zhang L, Zhuang Y, Zhao X, Niu H, Cheng JC-H, Zeng Z. Proteomic Profiling of Human Hepatic Stellate Cell Line LX2 Responses to Irradiation and TGF-β1. Journal of proteome research. 2019 Jan;18(1):508–521.
Journal cover image

Published In

Journal of proteome research

DOI

EISSN

1535-3907

ISSN

1535-3893

Publication Date

January 2019

Volume

18

Issue

1

Start / End Page

508 / 521

Related Subject Headings

  • X-Rays
  • Transforming Growth Factor beta1
  • Tandem Mass Spectrometry
  • Proteomics
  • Proteome
  • Liver Cirrhosis
  • Humans
  • Hepatic Stellate Cells
  • Gene Expression Regulation
  • Computational Biology