Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/82812
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | The c-Rel subunit of nuclear factor-κB regulates murine liver inflammation, wound-healing, and hepatocyte proliferation |
Other Titles: | The c-Rel subunit of nuclear factor-kappaB regulates murine liver inflammation, wound-healing, and hepatocyte proliferation |
Author: | Gieling, R. Elsharkawy, A. Caamano, J. Cowie, D. Wright, M. Ebrahimkhani, M. Burt, A. Mann, J. Raychaudhuri, P. Liou, H. Oakley, F. Mann, D. |
Citation: | Hepatology, 2010; 51(3):922-931 |
Publisher: | John Wiley & Sons Inc |
Issue Date: | 2010 |
ISSN: | 0270-9139 1527-3350 |
Statement of Responsibility: | Roben G. Gieling, Ahmed M. Elsharkawy, Jorge H. Caamaño, David E. Cowie, Matthew C. Wright, Mohammad R. Ebrahimkhani, Alastair D. Burt, Jelena Mann, Pradip Raychaudhuri, Hsiou-Chi Liou, Fiona Oakley and Derek A. Mann |
Abstract: | In this study, we determined the role of the nuclear factor-kappaB (NF-κB) subunit c-Rel in liver injury and regeneration. In response to toxic injury of the liver, c-Rel null (c-rel−/−) mice displayed a defect in the neutrophilic inflammatory response, associated with impaired induction of RANTES (Regulated upon Activation, Normal T-cell Expressed, and Secreted; also known as CCL5). The subsequent fibrogenic/wound-healing response to both chronic carbon tetrachloride and bile duct ligation induced injury was also impaired and this was associated with deficiencies in the expression of fibrogenic genes, collagen I and α-smooth muscle actin, by hepatic stellate cells. We additionally report that c-Rel is required for the normal proliferative regeneration of hepatocytes in response to toxic injury and partial hepatectomy. Absence of c-Rel was associated with blunted and delayed induction of forkhead box M1 (FoxM1) and its downstream targets cyclin B1 and Cdc25C. Furthermore, isolated c-rel−/− hepatocytes expressed reduced levels of FoxM1 and a reduced rate of basal and epidermal growth factor–induced DNA synthesis. Chromatin immunoprecipitation revealed that c-Rel binding to the FoxM1 promoter is induced in the regenerating liver. Conclusion: c-Rel has multiple functions in the control of liver homeostasis and regeneration and is a transcriptional regulator of FoxM1 and compensatory hepatocyte proliferation. |
Keywords: | Hepatocytes Animals Mice, Inbred C57BL Mice Hepatitis NF-kappa B Liver Regeneration Wound Healing Cell Proliferation Male |
Rights: | © 2009 American Association for the Study of Liver Diseases |
DOI: | 10.1002/hep.23385 |
Published version: | http://dx.doi.org/10.1002/hep.23385 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.