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Yan Lin,
Le-Xing Yu, He-Xin Yan,
Wen Yang,
Liang Tang,
Hui-Lu Zhang,
Qiong Liu,
Shan-Shan Zou,
Ya-Qin He,
Chao Wang,
Meng-Chao Wu,
Hong-Yang Wang
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ABSTRACT: Robust clinical and epidemiologic data support the role of inflammation as a key player in hepatocellular carcinoma (HCC) development. Our previous data showed that gut-derived lipopolysaccharide (LPS) promote HCC development by activating Toll-like receptor 4 (TLR4) expressed on myeloid-derived cells. However, the effects of gut-derived LPS on other types of liver injury models are yet to be studied. The purpose of this study was to determine the importance of gut-derived LPS and TLR4 signaling in a T-cell-mediated hepatitis-Con A-induced hepatitis model, which mimic the viral hepatitis. Reduction of endotoxin using antibiotics regimen or genetic ablation of TLR4 in mice significantly alleviate Con A-induced liver injury by inhibiting the infiltration of T lymphocytes into the liver and the activation of CD4(+) T lymphocytes as well as the production of T helper 1 cytokines; in contrast, exogenous LPS can promote Con A-induced hepatitis and CD4(+) T cells activation in vivo and in vitro. Reconstitution of TLR4-expressing myeloid cells in TLR4-deficient mice restored Con A-induced liver injury and inflammation, indicating the major cell target of LPS. In addition, TLR4 may positively regulate the target hepatocellular apoptosis via the perforin/granzyme B pathway. These data suggest that gut-derived LPS and TLR4 play important positive roles in Con A-induced hepatitis and modulation of the gut microbiotia may represent a new avenue for therapeutic intervention to treat acute hepatitis induced by hepatitis virus infection, thus to prevent hepatocellular carcinoma. Cancer Prev Res; 5(9); 1090-102. ©2012 AACR.
Cancer Prevention Research 05/2012; 5(9):1090-102. · 4.91 Impact Factor
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Hepatology 05/2011; · 11.66 Impact Factor
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Ying Jiang,
Wantao Ying,
Songfeng Wu,
Ming Chen,
Wei Guan,
Dong Yang,
Yanping Song,
Xin Liu,
Jianqi Li,
Yunwei Hao, [......],
Xueyong Li,
Jinpei Cheng,
Yanhua Liu,
Xianen Zhang,
Xiaofang Wang,
Jingdun Jia,
Daochang An,
Zhen Wang,
Qing Li,
Tuo Cui
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ABSTRACT: Herein we report proteome and transcriptome profiles of the human adult liver and present an initial analysis. Overall, the human liver proteome (HLP) dataset comprises 6,788 identified proteins with at least two peptides matches at 95% confidence, including 3,721 proteins newly identified in liver. The human liver transcriptome (HLT) dataset consists of 11,205 genes. The HLP is the largest proteome dataset for a human organ and is the first direct association between a proteome and its transcriptome derived from the same sample. Although it's hard to approach complete coverage of the HLP currently, several conclusions based on this dataset are clearly reached: 1) The 5,816 protein-encoding genes (PEGs) represented by the HLP and the 11,104 PEGs represented in the HLT have been identified from 20,070 PEGs in IPI Human v3.07 and 19,478 PEGs in the integrated human transcriptome database, respectively. 2) The patterns of chromosomal distribution of the genes corresponding to the HLP are highly consistent with those of the HLT. Some chromosomal regions, such as 16p13.3, 19q13.31, 19q13.42, and Xq28, exhibit particularly high densities of liver-specific genes, which perform the important functions related to normal physiology or/and pathology in this organ. 3) The HLP spans six orders of magnitude in relative protein abundance and 78% of the proteins fall in the middle of this range. Of newly identified liver proteins, 82.5% are of low abundance. 4) Proteins involving in metabolism, transport, and coagulation and those containing active domains for metabolism, transport, and biosynthesis are significantly enriched in liver. 5) All 94 metabolic pathways in KEGG are touched to different extent. Of which, for 48 pathways, particularly those involved in metabolism of carbohydrates and amino acids, more than 80% of the component proteins have been detected. The liver-specific pathways, such as those participating in metabolism of bile acid and bilirubin and in biotransformation, are identified with remarkably high coverage. A total of 31 members of the cytochrome P450 family are identified, four of which have been observed for the first time in human liver. 6) Transport proteins involving in energy metabolism and secretion of both protein and bile acid are highly abundant. Three ion channels are described for the first time in liver. 7) Eight hundred proteins related to signal transduction and primarily involving in cellular recognition, localization, communication, and inflammation are present in the HLP dataset. Insulin and adipocytokine pathways, which are involved in the regulation of glucose and fatty acids, are highly covered. 8) Transcription factors (309 in total) have been recognized at relatively low detection rates and abundance; however, transcription factors regulating gene expression related to transport, metabolism, and biosynthesis are detected at relatively higher coverage and the protein products of their target genes (100), such as metabolic enzymes and plasma proteins, are also identified. 9) The overlap between the human liver and plasma proteomes is particularly noteworthy in the coagulation/anticoagulation/fibrinolysis and complement system. There is a significant positive linear correlation between the abundance of coagulator proteins in liver and plasma.
Journal of Proteome Research 09/2009; · 5.11 Impact Factor
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ABSTRACT: PCP-2 is a member of receptor-like protein tyrosine phosphatase of the MAM domain family. To investigate which part of PCP-2 was involved in its interaction with beta-catenin, we constructed various deletion mutants of PCP-2. These PCP-2 mutants and wild-type PCP-2 were co-transfected into BHK-21 cells with beta-catenin individually. An in vivo binding assay revealed that the expression of wild-type PCP-2, PCP-2 deltaC1C2 (deleted PCP-2 without both PTP domains) and PCP-2 deltaC2 (deleted PCP-2 without the second PTP domain) could be immunoprecipitated by anti-catenin antibody in every co-transfection, but PCP-2 EXT (deleted PCP-2 without the juxtamembrane region and both PTP domains) was missing, which implied that PCP-2 and beta-catenin could associate directly and the juxtamembrane region in PCP-2 was sufficient for the process.
Science in China Series C Life Sciences 05/2005; 48(2):163-7. · 1.61 Impact Factor
