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Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2001

Selective ablation of retinoid X receptor alpha in hepatocytes impairs their lifespan and regenerative capacity

Résumé

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.

Domaines

Génétique

Dates et versions

hal-04118015 , version 1 (05-06-2023)

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Citer

Takeshi Imai, Ming Jiang, Philippe Kastner, Pierre Chambon, Daniel Metzger. Selective ablation of retinoid X receptor alpha in hepatocytes impairs their lifespan and regenerative capacity. Proceedings of the National Academy of Sciences of the United States of America, 2001, 98 (8), pp.4581-4586. ⟨10.1073/pnas.071056098⟩. ⟨hal-04118015⟩
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