Vitamin D3 up-regulated protein 1 deficiency accelerates liver regeneration after partial hepatectomy in mice

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Title
Vitamin D3 up-regulated protein 1 deficiency accelerates liver regeneration after partial hepatectomy in mice
Author(s)
Hyo Jung Kwon; Young Suk Won; Y D Yoon; Woon Kee YoonKi Hoan Nam; In Pyo Choi; D Y Kim; Hyoung-Chin Kim
Bibliographic Citation
Journal of Hepatology, vol. 54, no. 6, pp. 1168-1176
Publication Year
2011
Abstract
Background & Aims: Liver regeneration is a complicated process involving a variety of interacting factors. Vitamin D3 up-regulated protein 1 (VDUP1) is a potent growth suppressor that, upon over-expression, inhibits tumor cell proliferation and cell-cycle progression. Here, we investigated the function of VDUP1 in liver regeneration following hepatectomy in mice. Methods: Liver regeneration after 70% partial hepatectomy (PH) was compared in VDUP1 knockout (KO) and wild-type (WT) mice, and the activities of proliferative- and cell-cycle-related signaling pathways were measured. Results: Compared with WT mice, liver recovery was significantly accelerated in VDUP1 KO mice during the first day after PH, in association with increased DNA synthesis. Consistent with this observation, the expression levels of key cell-cycle regulatory proteins, including cyclin D, cyclin E, cyclin-dependent kinase 4 (CDK4), p21, and p27, were markedly altered in the livers of VDUP1 KO mice. Induction of growth factors and activation of proliferative signaling pathway components including extracellular signal-regulated kinase 1/2 (ERK1/2), Akt, glycogen synthase kinase 3β (GSK3β), mammalian target of rapamycin (mTOR), and p70S6 kinase (p70S6K), occurred much earlier and to a greater extent in VDUP1 KO mouse livers. In addition, primary hepatocytes isolated from VDUP1 KO mice displayed increased activation of ERK1/2 and Akt in response to HGF and TGF-α. Conclusions: Our results reveal an important role for VDUP1 in the regulation of proliferative signaling during liver regeneration. Altered activation of genes involved in ERK1/2 and Akt signaling pathways may explain the accelerated growth responses seen in VDUP1 KO mice.
Keyword
AktERK1/2Growth factorLiver regenerationVDUP1
ISSN
0168-8278
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.jhep.2010.09.025
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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