In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 8 ( 2001-04-10), p. 4581-4586
Abstract:
Retinoid X receptors (RXRs) are involved in a number of signaling
pathways as heterodimeric partners of numerous nuclear receptors. Hepatocytes express high levels of the RXRα isotype, as well as
several of its putative heterodimeric partners. Germ-line disruption (knockout) of RXRα has been shown to be lethal in
utero , thus precluding analysis of its function at later life
stages. Hepatocyte-specific disruption of RXRα during liver organogenesis has recently revealed that the presence of hepatocytes is not mandatory for the mouse, at least under normal mouse facility
conditions, even though a number of metabolic events are impaired [Wan, Y.-J., et al. (2000) Mol. Cell.
Biol . 20, 4436–4444]. However, it is unknown whether RXRα plays a role in the control of hepatocyte proliferation and lifespan.
Here, we report a detailed analysis of the liver of mice in which RXRα was selectively ablated in adult hepatocytes by using the
tamoxifen-inducible chimeric Cre recombinase system. Our results show that the lifespan of adult hepatocytes lacking RXRα is shorter than
that of their wild-type counterparts, whereas proliferative hepatocytes of regenerating liver exhibit an even shorter lifespan. These lifespan
shortenings are accompanied by increased polyploidy and multinuclearity. We conclude that RXRα plays important
cell-autonomous function(s) in the mechanism(s) involved in the lifespan of hepatocytes and liver regeneration.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.071056098
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2001
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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