| First Author | Liu HX | Year | 2014 |
| Journal | Biochem Pharmacol | Volume | 91 |
| Issue | 2 | Pages | 256-65 |
| PubMed ID | 25087568 | Mgi Jnum | J:215381 |
| Mgi Id | MGI:5605204 | Doi | 10.1016/j.bcp.2014.07.003 |
| Citation | Liu HX, et al. (2014) Retinoic acid regulates cell cycle genes and accelerates normal mouse liver regeneration. Biochem Pharmacol 91(2):256-65 |
| abstractText | All-trans retinoic acid (RA) is a potent inducer of regeneration. Because the liver is the principal site for storage and bioactivation of vitamin A, the current study examines the effect of RA in mouse hepatocyte proliferation and liver regeneration. Mice that received a single dose of RA (25mug/g) by oral gavage developed hepatomegaly with increased number of Ki67-positive cells and induced expression of cell cycle genes in the liver. DNA binding data revealed that RA receptors retinoic acid receptor beta (RARbeta) and retinoid x receptor alpha (RXRalpha) bound to cell cycle genes Cdk1, Cdk2, Cyclin B, Cyclin E, and Cdc25a in mice with and without RA treatment. In addition, RA treatment induced novel binding of RARbeta/RXRalpha to Cdk1, Cdk2, Cyclin D, and Cdk6 genes. All RARbeta/RXRalpha binding sites contained AGGTCA-like motifs. RA treatment also promoted liver regeneration after partial hepatectomy (PH). RA signaling was implicated in normal liver regeneration as the mRNA levels of RARbeta, Aldh1a2, Crabp1, and Crbp1 were all induced 1.5 days after PH during the active phase of hepatocyte proliferation. RA treatment prior to PH resulted in early up-regulation of RARbeta, Aldh1a2, Crabp1, and Crbp1, which was accompanied by an early induction of cell cycle genes. Western blotting for RARbeta, c-myc, Cyclin D, E, and A further supported the early induction of retinoid signal and cell proliferation by RA treatment. Taken together, our data suggest that RA may regulate cell cycle progression and accelerates liver regeneration. Such effect is associated with an early induction of RA signaling, which includes increased expression of the receptor, binding proteins, and processing enzyme for retinoids. |
