Phosphorylated Smad2 and Smad3 signaling: Shifting between tumor suppression and fibro-carcinogenesis in chronic hepatitis C
Article first published online: 4 MAR 2013
© 2013 The Japan Society of Hepatology
Volume 43, Issue 12, pages 1327–1342, December 2013
How to Cite
Yamaguchi, T., Matsuzaki, K., Inokuchi, R., Kawamura, R., Yoshida, K., Murata, M., Fujisawa, J., Fukushima, N., Sata, M., Kage, M., Nakashima, O., Tamori, A., Kawada, N., Tsuneyama, K., Dooley, S., Seki, T. and Okazaki, K. (2013), Phosphorylated Smad2 and Smad3 signaling: Shifting between tumor suppression and fibro-carcinogenesis in chronic hepatitis C. Hepatology Research, 43: 1327–1342. doi: 10.1111/hepr.12082
- Issue published online: 26 DEC 2013
- Article first published online: 4 MAR 2013
- Accepted manuscript online: 20 FEB 2013 02:59AM EST
- Manuscript Revised: 21 JAN 2013
- Manuscript Accepted: 21 JAN 2013
- Manuscript Received: 10 APR 2012
- Ministry of Education, Science and Culture of Japan
- German Research Foundation
Figure S1 Hepatocytes persistently affected by transforming growth factor (TGF)-β together with pro-inflammatory cytokines come to exhibit carcinogenic pSmad3L (Ser 208/213) and fibrogenic pSmad2L (Thr 220)/C signaling.
Figure S2 Phospho-Smad3 signaling after hepatitis C virus (HCV) clearance. (a) Chronic hepatitis C can be cured if patients are treated with interferon (IFN) therapy that terminates chronic inflammation by eradicating HCV populations. In chronic hepatitis C, pSmad3L signaling initially depends on presence of chronic inflammation: cessation of chronic inflammation restores hepatocytic tumor-suppressive pSmad3C signaling, as occurring in normal hepatocytes, from carcinogenic pSmad3L signaling. (b) Other patients with advanced fibrosis have evolved beyond dependence on inflammation. Their preneoplastic hepatocytes constitutively carry out carcinogenic pSmad3L signaling, possibly caused by genetic and epigenetic carcinogenic factors, despite a blunted inflammation.
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