Cell cycle-mediated regulation of hepatic regeneration

被引:42
作者
Ehrenfried, JA
Ko, TC
Thompson, EA
Evers, BM
机构
[1] UNIV TEXAS,MED BRANCH,DEPT SURG,GALVESTON,TX 77555
[2] UNIV TEXAS,MED BRANCH,DEPT HUMAN BIOL CHEM & GENET,GALVESTON,TX 77555
关键词
D O I
10.1016/S0039-6060(97)90334-2
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background. Hepatic regeneration after partial hepatectomy (PH) is characterized by a synchronous induction of normally quiescent hepatocytes to reenter the cell cycle, leading to a complete restoration of hepatic mass. Cell cycle progression requires activation of cyclin-dependent kinases (Cdks) that are regulated by cyclins and Cdk inhibitors. Methods. Protein expression of the cyclins (D-type and E), Cdks (Cdk2 and 4), and Cdk inhibitors (p21 and p27) was measured by Western blot after SHAM operation or PH in F344 rats. In addition, Cdk2-associated kinase activity was measured. Results. Rapid induction of D-type and E cyclins, as well as their catalytic partners, Cdk2 and Cdk4, occurred after PH in rats. Complexes containing cyclin E and Cdk2 assembled in the regenerating liver, leading to increased Cdk2-associated kinase activity. The regenerating liver returned to preresection weight by day 7, at which time the Cdk2 activity also returned to SHAM levels. Biphasic induction of the Cdk inhibitor p21 was observed; the first peak occurred as early as 6 hours after PH, with a subsequent peak in expression occurring at 24 to 72 hours after PH. Conclusions. Taken together these data support the concept that cyclins, Cdks, and Cdk inhibitors regulate cell cycle progression in the regenerating liver In addition, the induction of p21 at two time points suggests that this protein may regulate both early proliferation and subsequent inhibition of hepatocyte regeneration.
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页码:927 / 935
页数:9
相关论文
共 43 条
[1]   DISTINCT PATTERNS OF CYCLIN D1 REGULATION IN MODELS OF LIVER-REGENERATION AND HUMAN LIVER [J].
ALBRECHT, JH ;
HU, MY ;
CERRA, FB .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1995, 209 (02) :648-655
[2]   CYCLIN AND CYCLIN-DEPENDENT KINASE-1 MESSENGER-RNA EXPRESSION IN MODELS OF REGENERATING LIVER AND HUMAN LIVER-DISEASES [J].
ALBRECHT, JH ;
HOFFMAN, JS ;
KREN, BT ;
STEER, CJ .
AMERICAN JOURNAL OF PHYSIOLOGY, 1993, 265 (05) :G857-G864
[3]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[4]   TRANSFORMING GROWTH FACTOR-BETA MESSENGER-RNA INCREASES DURING LIVER-REGENERATION - A POSSIBLE PARACRINE MECHANISM OF GROWTH-REGULATION [J].
BRAUN, L ;
MEAD, JE ;
PANZICA, M ;
MIKUMO, R ;
BELL, GI ;
FAUSTO, N .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (05) :1539-1543
[5]   REGENERATION OF MAMMALIAN LIVER [J].
BUCHER, NLR .
INTERNATIONAL REVIEW OF CYTOLOGY-A SURVEY OF CELL BIOLOGY, 1963, 15 :245-300
[6]   TRANSFORMING GROWTH-FACTOR-BETA INDUCES THE CYCLIN-DEPENDENT KINASE INHIBITOR P21 THROUGH A P53-INDEPENDENT MECHANISM [J].
DATTO, MB ;
LI, Y ;
PANUS, JF ;
HOWE, DJ ;
XIONG, Y ;
WANG, XF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (12) :5545-5549
[7]   THE CYCLIN-DEPENDENT PROTEIN-KINASES AND THE CONTROL OF CELL-DIVISION .1. [J].
DOREE, M ;
GALAS, S .
FASEB JOURNAL, 1994, 8 (14) :1114-1121
[8]   ASSOCIATION OF HUMAN CYCLIN-E WITH A PERIODIC G(1)-S PHASE PROTEIN-KINASE [J].
DULIC, V ;
LEES, E ;
REED, SI .
SCIENCE, 1992, 257 (5078) :1958-1961
[9]   THE NEUROTENSIN GENE IS A DOWNSTREAM TARGET FOR RAS ACTIVATION [J].
EVERS, BM ;
ZHOU, ZC ;
CELANO, P ;
LI, J .
JOURNAL OF CLINICAL INVESTIGATION, 1995, 95 (06) :2822-2830
[10]  
FAUSTO N, 1989, LAB INVEST, V60, P4