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Jianhua Zhang
Jianhua Zhang
School of Chemical and Biomedical Engineering, College of Engineering, Nanyang Technological University, Singapore, Singapore
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Wei Ning Chen
Wei Ning Chen
School of Chemical and Biomedical Engineering, College of Engineering, Nanyang Technological University, Singapore, Singapore
School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyag Drive, Singapore, 637459, Singapore
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School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyag Drive, Singapore, 637459, Singapore
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Abstract
Chronic hepatitis B virus (HBV) carriers may develop hepatocellular carcinoma (HCC) by a wide range of mechanisms including angiogenesis. We show that HBV replication induces the expression of angiogenic proteins interleukin 6 (IL6) and cyclooxygenase-2 (Cox2). Interestingly, ibuprofen (a Cox2 inhibitor) is found to attenuate the levels of IL6 and Cox 2 which are induced by HBV replication.
The mechanism of attenuation of angiogenic proteins by ibuprofen was further investigated. Our results show that HBx is involved in the increase of the expression of Cox2 through the NFκB pathway. However, the expression of Cox2 is decreased when the HBx-expressing cells are incubated with ibuprofen. The contrasting effect of HBx on Cox2 is found to be determined by differential dimer formation among the members of the NFκB family of proteins, including NFκB, RelA, and C-rel. Specifically, HBx alone results in dimer formation between NFκB and RelA, while the combined presence of HBx and ibuprofen leads to the formation of NFκB and C-rel. Additional information on the interaction network involving HBx, ibuprofen, and NFκB pathways is revealed by two-dimensional liquid chromatography-tandem mass spectrometry proteomics analysis. Taken together, our findings provide new insights on the angiogenesis induced by HBV replication.
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| 2019 | |
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11 |
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0,220 |
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Medicine (miscellaneous) Q3 |
| Scopus Cite Score |
155/133=1,2 |
| Scopus Cite Score Rank |
General Medicine 199/529 (Q2) |
| Scopus SNIP |
0,343 |
| Scopus Cites |
206 |
| Scopus Documents |
23 |
| Interventional Medicine and Applied Science | |
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| Language | English |
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2009 |
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