| Category |
Gastroenterology & Hepatology |
| Manuscript Type |
Autobiography |
| Article Title |
Senescent human hepatocytes express a unique secretory phenotype and promote macrophage migration
|
| Manuscript Source |
Unsolicited Manuscript |
| All Author List |
Katharine M Irvine, Richard Skoien, Nilesh J Bokil, Michelle Melino, Gethin P Thomas, Dorothy Loo, Brian Gabrielli, Michelle M Hill, Matthew J Sweet, Andrew D Clouston and Elizabeth E Powell |
| Funding Agency and Grant Number |
| Funding Agency |
Grant Number |
| National Health and Medical Research Council of Australia (NHMRC) |
APP1044650 |
| National Health and Medical Research Council of Australia (NHMRC) |
APP1003108 |
| Queensland Government’s Smart State Health and Medical Research Fund |
|
| Princess Alexandra Hospital Research and Development Foundation and The Australian Liver Foundation; Irvine KM is the recipient of the Australian Liver Foundation Pauline Hall Fellowship |
|
| Powell EE is the recipient of an NHMRC Practitioner Fellowship |
APP1004242 |
| Sweet MJ is the recipient of an Australian Research Council (ARC) Future Fellowship |
FT100100657 |
| an honorary NHMRC Senior Research Fellowship |
APP1003470 |
| Hill MM is the recipient of an ARC Future Fellowship |
FT120100251 |
| Hill MM is the recipient of an ARC Future Fellowship |
FT120100251 |
|
| Corresponding Author |
Elizabeth E Powell, Professor, Director, Centre for Liver Disease Research, School of Medicine, The University of Queensland, Translational Research Institute, Brisbane, 37 Kent St, Woolloongabba, 4102 Brisbane, Australia. e.powell@uq.edu.au |
| Key Words |
Cell aging; Chemokines; Hepatocytes; Inflammation; Liver diseases; Macrophages |
| Core Tip |
Hepatocyte senescence is observed in all chronic liver diseases of hepatocellular origin, even at early stages of disease progression. Although widely studied in cancer biology, the role of cellular senescence in the pathogenesis of inflammatory diseases is not known. We developed a novel model of stress-induced hepatocyte senescence and used it to demonstrate that senescent human hepatocytes adopt a hyper-secretory phenotype, which is likely to condition their microenvironment and contribute to disease pathogenesis. We used microarray and proteomic analysis to characterise senescent hepatocytes and identify candidate mediators; and confirmed the functional relevance of senescence-associated secretory phenotype by demonstrating that conditioned media from senescent hepatocytes elicits inflammatory macrophage migration. |
| Publish Date |
2014-12-20 19:42 |
| Citation |
Irvine KM, Skoien R, Bokil NJ, Melino M, Thomas GP, Loo D, Gabrielli B, Hill MM, Sweet MJ, Clouston AD, Powell EE. Senescent human hepatocytes express a unique secretory phenotype and promote macrophage migration. World J Gastroenterol 2014; 20(47): 17851-17862 |
| URL |
http://www.wjgnet.com/1007-9327/full/v20/i47/17851.htm |
| DOI |
http://dx.doi.org/10.3748/wjg.v20.i47.17851 |
