PMID- 11287642
OWN - NLM
STAT- MEDLINE
DCOM- 20010510
LR  - 20220331
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 98
IP  - 8
DP  - 2001 Apr 10
TI  - Selective ablation of retinoid X receptor alpha in hepatocytes impairs their 
      lifespan and regenerative capacity.
PG  - 4581-6
AB  - 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 RXRalpha isotype, as well as several of its putative heterodimeric 
      partners. Germ-line disruption (knockout) of RXRalpha has been shown to be lethal 
      in utero, thus precluding analysis of its function at later life stages. 
      Hepatocyte-specific disruption of RXRalpha 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 RXRalpha plays a role in the control 
      of hepatocyte proliferation and lifespan. Here, we report a detailed analysis of 
      the liver of mice in which RXRalpha 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 RXRalpha 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 
      RXRalpha plays important cell-autonomous function(s) in the mechanism(s) involved 
      in the lifespan of hepatocytes and liver regeneration.
FAU - Imai, T
AU  - Imai T
AD  - Institut de Genetique et de Biologie Moleculaire et Cellulaire, College de 
      France, BP 163, 67404 Illkirch Cedex, Communaute Urbaine de Strasbourg, France.
FAU - Jiang, M
AU  - Jiang M
FAU - Kastner, P
AU  - Kastner P
FAU - Chambon, P
AU  - Chambon P
FAU - Metzger, D
AU  - Metzger D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20010403
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - *Cellular Senescence
MH  - Hepatectomy
MH  - Hepatocytes/cytology/*metabolism
MH  - *Liver Regeneration
MH  - Mice
MH  - Mice, Knockout
MH  - Receptors, Retinoic Acid/genetics/*physiology
MH  - Retinoid X Receptors
MH  - Transcription Factors/genetics/*physiology
PMC - PMC31877
EDAT- 2001/04/05 10:00
MHDA- 2001/05/22 10:01
PMCR- 2001/10/10
CRDT- 2001/04/05 10:00
PHST- 2001/04/05 10:00 [pubmed]
PHST- 2001/05/22 10:01 [medline]
PHST- 2001/04/05 10:00 [entrez]
PHST- 2001/10/10 00:00 [pmc-release]
AID - 071056098 [pii]
AID - 0560 [pii]
AID - 10.1073/pnas.071056098 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4581-6. doi: 10.1073/pnas.071056098. 
      Epub 2001 Apr 3.