Abstract:
BACKGROUND/AIMS:We reported massive liver repopulation by transplanted hepatocytes in rats given retrorsine (RS), a pyrrolizidine alkaloid which blocks proliferation of resident cells. In these studies, molecular alterations induced by RS on hepatocyte cell cycle were investigated. METHODS:Animals were treated according to the protocol for liver repopulation, i.e. two injections of RS (30 mg/kg) followed by two-thirds partial hepatectomy (PH) and were sacrificed at various time points thereafter. Livers were analyzed for the expression of cell cycle-related genes. RESULTS:Prior to PH, increased cyclin D1 mRNA and protein levels were found in livers of RS-treated rats. Expression of PCNA was also increased; however, DNA synthesis was not significantly changed. Other cyclins, including cyclin B and cyclin E, were not induced. Cyclin D1 expression increased in controls post-PH and then declined by 48 h, as expected. By contrast, no such modulation of cyclin D1 levels was seen in RS group receiving PH and expression remained high at 48 h, without mitotic division. CONCLUSIONS:Exposure to RS is able to block cell cycle progression after cyclin D1 and PCNA induction, but prior to S phase. Such persistent block outside the resting phase may contribute to the selective replacement of resident cells during liver repopulation.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Pitzalis S,Doratiotto S,Greco M,Montisci S,Pasciu D,Porcu G,Pani P,Laconi S,Laconi Edoi
10.1016/j.jhep.2005.03.029subject
Has Abstractpub_date
2005-09-01 00:00:00pages
485-90issue
3eissn
0168-8278issn
1600-0641pii
S0168-8278(05)00313-2journal_volume
43pub_type
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更新日期:1998-10-01 00:00:00
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pub_type: 杂志文章,meta分析,评审
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更新日期:2009-07-01 00:00:00
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,随机对照试验
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pub_type: 杂志文章,多中心研究
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