Relationships between deficits in tissue mass and transcriptional programs after partial hepatectomy in mice.
Liver regeneration after two-thirds partial hepatectomy (2/3 PH) results in synchronized proliferation of hepatocytes and rapid restoration of liver mass. Understanding the mechanisms that regulate this process has both biological and clinical importance. Using cDNA microarray analysis, we investigated whether gene activation after 2/3 PH is specifically related to liver growth and hepatocyte proliferation. We generated gene expression profiles at 4, 12, 20, and 30 hours after 2/3 PH and compared them with profiles obtained at the same time points after 1/3 PH, a procedure that causes minimal DNA replication. Surprisingly, a significant number of genes whose expression is altered after 2/3 PH are similarly up- or down-regulated after 1/3 PH, particularly at 4 hours. We identified a number of genes and transcription factors that are more highly expressed ("preferential expression") after 2/3 PH and show that a shift in transcriptional programs in the regenerating liver occurs between 4 and 12 hours after 2/3 PH, a time at which the decision to replicate appears to be made. These results show that the liver responds to PH with massive changes of gene expression, even in the absence of DNA replication. We suggest that the changes in gene expression during the first 4 to 6 hours after 2/3 PH may induce chromatin remodeling and facilitate the binding of new sets of transcription factors required for DNA replication.
Li
Jiangning
J
Department of Pathology, School of Medicine, University of Washington, Seattle, WA 98195, USA.
Campbell
Jean S
JS
Mitchell
Claudia
C
McMahan
Ryan S
RS
Yu
Xuesong
X
Riehle
Kimberly J
KJ
Bumgarner
Roger E
RE
Fausto
Nelson
N
D000818:Animals; D002452:Cell Count; D049109:Cell Proliferation; D042002:Chromatin Assembly and Disassembly; D004261:DNA Replication; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006498:Hepatectomy; D008099:Liver / Q000502:physiology*; D008115:Liver Regeneration / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D013997:Time Factors; D014158:Transcription, Genetic
Cancer Res. 1964 Oct;24:1611-25
14234005
Nature. 2002 Dec 5;420(6915):563-73
12466851
Mol Biol Cell. 2007 Oct;18(10):4085-95
17699597
Genome Biol. 2003;4(1):R7
12540299
Nat Rev Mol Cell Biol. 2004 Oct;5(10):836-47
15459664
Hepatology. 2007 Jun;45(6):1471-7
17427161
Int J Biochem Cell Biol. 2007;39(4):842-50
17317269
Genome Biol. 2003;4(4):R28
12702209
Am J Physiol. 1997 Oct;273(4):G905-12
9357834
Cell Cycle. 2008 Jul 15;7(14):2215-24
18635970
Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11181-6
12177410
BMC Genomics. 2008 Nov 06;9:527
18990226
Proc Natl Acad Sci U S A. 2004 Mar 30;101(13):4477-82
15070743
Genes Dev. 2006 Aug 15;20(16):2306-14
16912279
BMC Genomics. 2004 Nov 08;5:87
15533245
J Clin Invest. 1998 Sep 1;102(5):996-1007
9727068
J Hepatol. 2003 Jun;38(6):784-92
12763372
J Biol Chem. 2005 Feb 4;280(5):3715-22
15546871
J Biol Chem. 2007 Apr 13;282(15):11197-204
17227769
Cell Cycle. 2009 May 15;8(10):1621-9
19377303
Hepatology. 2004 Jun;39(6):1477-87
15185286
J Leukoc Biol. 2007 Jan;81(1):328-35
17046970
Mol Cell Biol. 2006 Jan;26(1):155-68
16354687
Liver Transpl. 2008 Dec;14(12):1718-24
19025926
Microsurgery. 2006;26(6):465-9
16924633
Transplantation. 2003 Jul 15;76(1):5-10
12865779
Nat Genet. 2000 May;25(1):25-9
10802651
Hepatology. 2006 Feb;43(2 Suppl 1):S45-53
16447274
Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10608-13
15249655
Hepatology. 2002 Mar;35(3):525-34
11870364
Nat Genet. 2002 May;31(1):19-20
11984561
Biotechniques. 2003 Feb;34(2):374-8
12613259
J Cell Physiol. 2007 Nov;213(2):286-300
17559071
OMICS. 2003 Fall;7(3):235-52
14583114
J Biol Chem. 2005 Jan 28;280(4):2562-8
15536070
C R Biol. 2003 Oct-Nov;326(10-11):1021-30
14744109
Nucleic Acids Res. 2003 Jan 1;31(1):219-23
12519986
Genome Biol. 2003;4(10):R70
14519205
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3663-7
11891324
Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5116-21
11309499