Expression patterns and action analysis of genes associated with physiological responses during rat liver regeneration: Innate immune response.
ABSTRACT To study the relationship between innate immune response and liver regeneration (LR) at transcriptional level.
Genes associated with innate immunity response were obtained by collecting the data from databases and retrieving articles. Gene expression changes in rat regenerating liver were detected by rat genome 230 2.0 array.
A total of 85 genes were found to be associated with LR. The initially and totally expressed number of genes at the phases of initiation [0.5-4 h after partial hepatectomy (PH)], transition from G0 to G1 (4-6 h after PH), cell proliferation (6-66 h after PH), cell differentiation and structure-function reconstruction (66-168 h after PH) was 36, 9, 47, 4 and 36, 26, 78, 50, respectively, illustrating that the associated genes were mainly triggered at the initial phase of LR and worked at different phases. According to their expression similarity, these genes were classified into 5 types: 41 up-regulated, 4 predominantly up-regulated, 26 down-regulated, 6 predominantly down-regulated, and 8 approximately up/down-regulated genes, respectively. The expression of these genes was up-regulated 350 times and down-regulated 129 times respectively, demonstrating that the expression of most genes was enhanced while the expression of a small number of genes was decreased during LR. Their time relevance was classified into 14 groups, showing that the cellular physiological and biochemical activities during LR were staggered. According to the gene expression patterns, they were classified into 28 types, indicating that the cellular physiological and biochemical activities were diverse and complicated during LR.
Congenital cellular immunity is enhanced mainly in the forepart, prophase and anaphase of LR while congenital molecular immunity is increased dominantly in the forepart and anaphase of LR. A total of 85 genes associated with LR play an important role in innate immunity.
-
Citations (0)
-
Cited In (0)
Page 1
PO Box 2345, Beijing 100023, China World J Gastroenterol 2006 December 28; 12(48): 7852-7858
www.wjgnet.com World Journal of Gastroenterology ISSN 1007-9327
wjg@wjgnet.com © 2006 The WJG Press. All rights reserved.
Expression patterns and action analysis of genes associated
with physiological responses during rat liver regeneration:
Innate immune response
Guang-Wen Chen, Ming-Zhen Zhang, Li-Feng Zhao, Cun-Shuan Xu
www.wjgnet.com
RAPID COMMUNICATION
Guang-Wen Chen, College of Life Science, Lanzhou University,
Lanzhou 730000, Gansu Province, China
Guang-Wen Chen, Ming-Zhen Zhang, Cun-Shuan Xu, College
of Life Science, Henan Normal University, Xinxiang 453007,
Henan Province, China
Li-Feng Zhao, Key Laboratory for Cell Differentiation Regu-
lation, Xinxiang 453007, Henan Province, China
Supported by the National Natural Science Foundation of China,
No. 30270673
Correspondence to: Professor Cun-Shuan Xu, College of Life
Science, Henan Normal University, Xinxiang 453007, Henan
Province, China. xucs@x263.net
Telephone: +86-373-3326001 Fax: +86-373-3326524
Received: 2006-08-25 Accepted: 2006-10-09
Abstrac t
AIM: To study the relationship between innate immune
response and liver regeneration (LR) at transcriptional
level.
METHODS: Genes associated with innate immunity
response were obtained by collecting the data from
databases and retrieving articles. Gene expression
changes in rat regenerating liver were detected by rat
genome 230 2.0 array.
RESULTS: A total of 85 genes were found to be
associated with LR. The initially and totally expressed
number of genes at the phases of initiation [0.5-4 h
after partial hepatectomy (PH)], transition from G0 to
G1 (4-6 h after PH), cell proliferation (6-66 h after PH),
cell differentiation and structure-function reconstruction
(66-168 h after PH) was 36, 9, 47, 4 and 36, 26, 78,
50, respectively, illustrating that the associated genes
were mainly triggered at the initial phase of LR and
worked at different phases. According to their expression
similarity, these genes were classifi ed into 5 types: 41
up-regulated, 4 predominantly up-regulated, 26 down-
regulated, 6 predominantly down-regulated, and 8
approximately up/down-regulated genes, respectively.
The expression of these genes was up-regulated 350
times and down-regulated 129 times respectively,
demonstrating that the expression of most genes was
enhanced while the expression of a small number of
genes was decreased during LR. Their time relevance
was classifi ed into 14 groups, showing that the cellular
physiological and biochemical activities during LR were
staggered. According to the gene expression patterns,
they were classified into 28 types, indicating that the
cellular physiological and biochemical activities were
diverse and complicated during LR.
CONCLUSION: Congenital cellular immunity is
enhanced mainly in the forepart, prophase and anaphase
of LR while congenital molecular immunity is increased
dominantly in the forepart and anaphase of LR. A total
of 85 genes associated with LR play an important role in
innate immunity.
© 2006 The WJG Press. All rights reserved.
Key words: Partial hepatectomy; Rat genome 230 2.0
array; Innate immune response; Genes associated with
liver regeneration
Chen GW, Zhang MZ, Zhao LF, Xu CS. Expression patterns
and action analysis of genes associated with physiological
responses during rat liver regeneration: Innate immune
response. World J Gastroenterol 2006; 12(48): 7852-7858
http://www.wjgnet.com/1007-9327/12/7852.asp
INTRODUCTION
Organisms can resist and remove endogenous and
exogenous poisons via their innate immune cells and
other factors. This process is known as innate immune
response[1], a self-protection mechanism of living
organisms which is absolutely indispensable to their
survival[2]. Innate immune responses consist of three parts,
namely barrier of self-tissue, innate cellular immunity and
innate molecular immunity. Tissue barrier can excrete
antibacterial and bactericidal matters to kill pathogens,
innate cellular immunity can not only remove pathogens
invading body via immune cells but also clear the broken,
dead and abnormal cells, while innate molecular immunity
can demolish and dissolve injurious substances via active
molecules and cytokines[3]. Liver containing NK cells,
T lymphocytes, macrophages, etc, is an important organ
where innate immune response takes place[4]. After partial
hepatectomy (PH), liver undergoes severe injury. How the
remnant liver cells are protected by the innate immune
system deserves intensive study[5].
In addition, PH[6] can activate the remaining
hepatocytes to rapidly proliferate and compensate for the
Page 2
Chen GW et al. Action of innate immune response-related genes on rat LR 7853
www.wjgnet.com
loss of liver mass, which is known as liver regeneration
(LR)[7,8]. Based on the cellular physiological activities, the
regeneration proceeding is usually categorized into four
stages: initiation (0.5-4 h after PH), transition from G0 to
G1 (4-6 h after PH), cell proliferation (6-66 h after PH),
cell differentiation and reorganization of the structure-
function (66-168 h after PH)[8]. According to the time
course, it can be classified into four phases: forepart
(0.5-4 h after PH), prophase (6-12 h after PH), metaphase
(16-66 h after PH), and anaphase (72-168 h after PH)[9],
involving many physiological and biochemical events, such
as cell activation, cell de-differentiation, cell proliferation
and its regulation, cell re-differentiation, reorganization
of structure-function[10], which are regulated by many
factors including innate immune response. The action of
genes associated with liver diseases caused by hepatitis
virus infection and pathogen infection during LR, has
been analyzed[11-13]. In the present study, rat genome 230
2.0 array containing 151 genes involved in innate immune
response was used to detect the gene expression changes
in regenerating liver after 2/3 hepatectomy as previously
described[14-17] in order to investigate the relevance between
LR and innate immune response at transcriptional level.
The expression changes, patterns and action of these
genes during LR were primarily analyzed. Our results
indicate that 85 out of the 151 genes are associated with
LR[18].
MATERIALS AND METHODS
Regenerating liver preparation
Healthy SD rats weighing 200-250 g were obtained
from the Animal Center of Henan Normal University.
The rats were divided into groups at random, 6 rats in
each group (male: female = 1:1). PH was performed as
previously described[6], the left and middle lobes of liver
were removed. The rats were killed by cervical vertebra
dislocation at 0.5, 1, 2, 4, 6, 8, 12, 16, 18, 24, 30, 36, 42,
48, 54, 60, 66, 72, 96, 120, 144 and 168 h after PH and the
regenerating livers were observed at corresponding time
points. The livers were rinsed three times in PBS at 4℃,
then 100-200 mg liver tissue was taken from middle part
of the right lobe. Six samples were collected from each
group and mixed into 1-2 g (0.1-0.2 g × 6) liver tissue,
then stored at -80℃. The sham-operation (SO) groups
underwent the same PH without removal of the liver
lobes. The animal protection laws of China were strictly
followed.
RNA isolation and purifi cation
Total RNA was isolated from frozen livers according to
the manual of Trizol kit (Invittrogen)[19] and then purifi ed
based on the guide of RNeasy mini kit (Qiagen)[20].
Agarose electrophoresis (180V, 0.5h) showed that total
RNA sample exhibited a 2:1 ratio of 28S to 18S rRNA
intensities. Total RNA concentration and purity were
estimated by optical density measurements at 260/280
nm[21].
cDNA, cRNA synthesis and purifi cation
Total RNA (1-8 μg) was used as a template for cDNA
synthesis. cDNA and cRNA synthesis was proceeded as
previously described[16]. cRNA labeled with biotin was
synthesized using 12 μL synthesized cDNA as a template,
cDNA and cRNA were purifid[16]. Measurement of
concentration, purity and quality of cDNA and cRNA was
performed as previously reported[21].
cRNA fragmentation and microarray detection
Fifteen μL (1 μg/μL) cRNA incubated with 5 ×
fragmentation buffer at 94℃ for 35 min was digested
into 35-200 bp fragments. The hybridization buffer was
added to the prehybridized Rat Genome 230 2.0 microarry
produced by Affymetrix, and then hybridization was
carried out for 16 h at 45℃ on a rotary mixer at 60 rpm.
The microarray was washed and stained by GeneChip
fl uidics station 450 (Affymetrix Inc., USA). The chips were
scanned by GeneChip scan 3000 (Affymetrix Inc., USA),
and the signal values of gene expression were observed[17].
Microarray data analysis
The normalized signal values, signal detections (P, A, M)
and experiment/control (Ri) were obtained by quantifying
and normalizing the signal values using GCOS1.2[17].
Normalisation of microarray data
To minimize the errors in microarray analysis, each
analysis was performed three times by rat genome 230
2.0 microarray. Results with a maximal total ratio (Rm)
and an average of three housekeeping genes β-actin,
hexokinase and glyseraldehyde-3-phosphate dehydrogenase
approaching 1.0 (Rh) were taken as a reference. Modifi ed
data were generated by applying a correction factor
(Rm/Rh) multiplying the ratio of every gene in Rh at each
time point. To remove spurious gene expression changes
resulting from errors in the microarray analysis, the gene
expression profiles at 0-4 h, 6-12 h and 12-24 h after
PH were reorganized by normalization analysis program
(NAP) software according to the cell cycle progression
of regenerating hepatocytes. Data statistics and cluster
analysis were done using the GeneMath, GeneSpring,
Microsoft Excel softwares[17,22,23].
Identifi cation of genes associated with liver regeneration
First, the nomenclature of innate immune response was
adopted from the GENEONTOLOGY database (www.
geneontology.org) and input into NCBI (www.ncbi.nlm.
nih.gov) and RGD (rgd.mcw.edu) to identify the rat, mouse
and human genes associated with the biological process.
According to the maps of biological pathways embodied
by GENMAPP (www.genmapp.org), KEGG (www.
genome.jp /kegg/pathway.html#amino) and BIOCARTA
(www.biocarta.com/genes/index.asp), genes associated
with innate immune response were collated. The results
of this analysis were codified and compared with those
obtained for humans and mice in order to identify human
and mouse genes which are different from those of rats.
Comparing these genes with the analysis output of rat
genome 230 2.0 array, genes showing more than twofold
change in expression level as meaningful expression
changes[18], were referred to as rat homologous or rat
specific genes associated with innate immune response
Page 3
under evaluation. Genes displaying reproducible results in
three independent analyses with the chip and more than
twofold change in expression level at least at one time
point during LR with a signifi cant difference (P ≤ 0.01<
0.05) or an extremely significant difference (P ≤ 0.01)
between PH and SO, were referred to as genes associated
with liver regeneration.
RESULTS
Expression changes of innate immune
response-associated genes during liver regeneration
According to the data from databases at NCBI,
GENEMAP, KEGG and BIOCARTA, a total of 275
genes are involved in innate immune response, of which
151 are contained in the rat genome 230 2.0 array. In the
resent study, 85 out of these 151 genes revealed meaningful
expression changes at least at one time point after PH,
showing a signifi cant difference or an extremely signifi cant
difference in expression when PH was compared with SO
and reproducible results checked by three detects with
rat genome 230 2.0 array, suggesting that the genes were
associated with LR. Their expression was up-regulated
2 to 128 times and down-regulated 2 to 10 times of the
control (Table 1). The expression was up-regulated in
41, down-regulated in 26, and up/down-regulated in 18
genes, respectively, during LR. The expression of these
85 genes was up-regulated 350 times and down-regulated
129 times (Figure 1A). At the initiation stage of LR (0.5-4
h after PH), the expression was up-regulated in 28 and
down-regulated in 8 genes. At the transition phase from
G0 to G1 (4-6 h after PH), 21 was up-regulated in 21 and
down-regulated in 5 genes. At cell proliferation period
(6-66 h after PH), the expression was up-regulated in 42,
down-regulated in 29, and up/down-regulated in 8 genes,
respectively. At cell differentiation and reorganization
of the structure-function stage (66-168 h after PH), the
expression was up-regulated in 32, down-regulated in 14,
and up/down-regulated in 4 genes, respectively (Figure 1B).
Initiation expression time of innate immune response-
associated genes during liver regeneration
At each time point of LR, the number of initially and
totally up-regulated, down-regulated genes respectively
was both 10 and 2 at 0.5 h; 7,6 and 15, 6 at 1 h; 7, 0 and
18, 1 at 2 h; 4, 0 and 20, 1 at 4 h; 1, 4 and 14, 5 at 6 h; 0,
0 and 16, 3 at 8 h ; 1, 0 and 19, 3 at 12 h ; 7, 4 and 19, 4
at 16 h ; 3, 9 and 19, 14 at 18 h ; 1, 0 and 17, 14 at 24 h ;
0, 3 and 12, 8 at 30 h ; 1, 3 and 19, 9 at 36 h ; 1, 1 and 15,
5 at 42 h ; 2, 1 and 26, 12 at 48 h; 0, 2 and 15, 11 at 54 h ;
0, 1 and 16, 7 at 60 h ; 0, 0 and 12, 4 at 66 h ; 0, 0 and 10,
4 at 72 h ; 1, 0 and 14, 7 at 96 h ; 3, 0 and 18, 6 at 120 h ;
0, 0 and 12, 5 at 144 h ; 0, 0 and 14, 6 at 166 h (Figure 2).
Generally, gene expression changes occurred during the
Table 1 Expression of 85 innate immune response-associated genes during rat liver regeneration
Gene Abbr. Associated
to others
Fold
difference
Gene Abbr. Associated
to others
Fold
difference
Gene Abbr. Associated
to others
Fold
difference
Gene Abbr. Associated
to others
Fold
difference
Innate immune cells
1 Macrophage
Adora2a
Anxa1
Cebpb
Clec7a
Cybb
Ereg
Ltb4r
Mif
Pap
Pla2g4a
Ptgs2
S100a8
S100a9
Tgfb1
2 NK cell
Ncr3
Ptger3
Rela
Ripk2
Tlr2
Tlr4
3 Other cells
Aoc3
Atrn
Clu
Colec12
Crp
Hrh1
Hrh4
Mcpt6
Nr3c1
Spp1
Nfatc4
Innate immune effectors
4 Complement system
C1qa
C1qr1
C2
1C3
C3ar1
C4a
C4bpa
C5ar1
Cfh
Cfi
Cr2
Crry
Masp1
Mbl2
5 Cell factors
a Interlenkin and related factors
Bcl31
3.9
0.5
0.5, 9.9
7.5
0.2
4.7
0.5, 2.7
0.5
Bdkrb2
1Il1b
Il1f5
Il1r1
Il1rn
Il2
Il5
Sarm1
Sele
b Interferon and related factors
Ifnk
Ddx58
Irf3
Mx2
c Iumor necrosis factor and related factors Reg3a
Ager
Myd88
Tnf 1
d Chemotactic numerator and telated factors
Ccl17
Ccl19
Ccl2
Ccl20
Ccl24
1Ccl4
Ccl7
Ccr1
3
1
1
1
1
0.4
0.4
0.4, 2.8
0.5
16.3
0.3, 3.5
3.5
0.2, 4.3
12.9
Cxcl10
Cxcl12
Darc
Others
Parp4
Alox5
Alox5ap
Apoe
Casp12
Dmbt1
Hck
Map2k3
Prkca
Ptafr
0.3, 9.2
0.2
0.4, 8.50.5
4.3
3.1
0.2
2.5
0.4
0.5, 8.7
3.2
68.6
2
0.1, 2.1
6.5
4.9
4.0
1
1
1, 2 0.5
0.2, 2.5
4.9
0.1
0.4,2.6
9.8
0.4
0.4
4.6
7.1
0.1, 64.1
0.3, 7.5
2
3
0.3
5.5
2.1
0.2
0.3, 2.3
0.5
2.0
0.4, 2.6
2.5
6.4
6.0
2.4
3.0
0.2
0.1, 5.7
11.8
2.6
9.4
1, 2
2, 3 0.4
2.1
3.2
Reg3g
0.3
0.2
0.5
0.4
10.6
0.5
0.1
3.9
128.0
8.0
4.0
0.2, 3.0
22.6
0.4,.24.9
3
1
1
1, 2
6.1
4.4
3.0 0.4
1Reported genes associated with liver regeneration; associated to others: genes are involved in another kind of the responses besides one kind of innate immune
responses; others: other genes associated with innate immune response, but cannot be clearly categorized.
www.wjgnet.com
7854 ISSN 1007-9327 CN 14-1219/R World J Gastroenterol December 28, 2006 Volume 12 Number 48
Page 4
whole LR. The expression of these genes was up-regulated
350 times and down-regulated 129 times. The expression
of the genes was predominantly initially up-regulated in
the forepart, and initially down-regulated in the prophase
and metaphase, whereas the initial expression of very few
genes was observed in the anaphase.
Expression similarity and time relevance of innate immune
response-associated genes during liver regeneration
Based on their similar expression, the 85 genes during LR
could be divided into 41 up-regulated, 4 predominantly
up-regulated, 26 down-regulated, 6 predominantly down-
regulated, and 8 up/down-regulated genes, respectively
(Figure 3). Based on their time relevance, they could also
be classifi ed into 14 groups (0.5 h, 1 and 66 h, 2 h, 4 and 8
h, 12 and 36 h, 16 and 96 h, 18 and 24 h, 30 and 42 h, 48
h, 54 and 60 h, 72 h, 120 h, 144 and 168 h), in which their
expression was up- and down-regulated at 10 and 2 h, 27
and 10 h, 18 and 1 h, 20 and 1 h, 30 and 8 h, 38 and 12 h,
33 and 11 h, 36 and 20 h, 26 and 12 h, 31 and 18 h, 10 and
4 h, 18 and 6 h, 26 and 11 h (Figure 3). The up-regulated
expression of genes was mainly associated with cellular
immunity. The down-regulated expression of genes was
signifi cantly associated with molecular immunity.
Expression patterns of innate immune
response-associated genes during liver regeneration
According to their expression changes during LR, the
patterns of the above 85 genes might be categorized into
28 types: 5 up-regulated genes at one time point, i.e. at 4,
48, 96, 120 h after PH (Figure 4A); 4 up-regulated genes at
two time points, i.e. at 12 and 60 h, 42 and 120 h, 16 and
42 h (Figure 4B); 1 up-regulated gene at three time points
(Figure 4B); 5 up-regulated genes at more time points
(Figure 4B); 3 up-regulated genes at one phase, i.e. at 0.5-8
h, 4-8 h, 120-168 h (Figure 4C); 1 up-regulated gene at two
phases, i.e. at 16-36 h, 42-48 h (Figure 4C); 1 up-regulated
gene at three phases (Figure 4C); 1 up-regulated gene at
more phases (Figure 4C); 1 up-regulated gene at one time
point/one phase, i.e. at 120 and 2-72 h, 48 and 2-24 h, 18
and 48-60 h, 42 and 120-168 h (Figure 4D); 1 up-regulated
gene at two time points/three phases (Figure 4E); 1 up-
regulated gene at two time points/one phase (Figure 4E);
1 up-regulated at one time point/ three phases (Figure 4E); 1
up-regulated gene at two time points/three phases (Figure
4E); 3 up-regulated genes at two time points/two phases
(Figure 4E); 1 up-regulated gene at three time points/
one phase (Figure 4F); 1 up-regulated gene at three time
points/two phases (Figure 4F); 3 up-regulated genes at
Figure 1 Expression frequency (A) and changes (B) of 85 innate im m une response-associated genes during rat liver regeneration. Data detected by rat genom e 230 2.0
array were analyzed and graphed by Microsoft Excel. The dots above bias indicate that the expression of genes was increased m ore than two folds and up-regulated 350
tim es, the dots under bias indicate that the expression of genes was decreased m ore than two folds and down-regulated 129 tim es, the dots between biases indicate that
the expression of genes has no alteration. The expression of 59 genes was increased 2-128 folds, while the expression of 44 genes was increased 2-10 folds.
Signal value (sample)
105
104
103
102
10
1
Gene expression levels
3.0
2.5
2.0
1.5
1.0
0.5
0.0
-0.5
-1.0
-1.50 4 812 18 24 3036 42 48 5460 66 72 96 120 144 168
Recovery time after partial hepatectomy (h)
1 10 102 103 104 105
Signal value (control)
A
B
Expressing gene numbers
40
35
30
25
20
15
10
5
00.5 1 2 4 6 8 12 16 18 24 30 36 42 48 54 60 66 72 96 120144 168
Recovery time after partial hepatectomy (h)
Figure 2 Initial and total expression profiles of 85 innate im m une
response-associated genes at each tim e point of liver regeneration.
Grey bars: up-regulated expression gene; white bars: down-regulated
expression gene; blank bars: initially expressed genes in which up-
regulated genes are predom inant in the forepart, and down-regulated
genes in the prophase and metaphase, whereas very few in the
anaphase; dotted bars: the total num ber of expressed genes, in which
the expression of som e genes is up-regulated and the expression of
others is down-regulated during LR.
Chen GW et al. Action of innate immune response-related genes on rat LR 7855
www.wjgnet.com
Page 5
more phases (Figure 4F); 11 down-regulated genes at one
time point, i.e. 0.5, 6, 16, 18, 30, 36, 42, 48, 54, 60 h (Figure
4G); 5 down-regulated genes at two time points, i.e. at 0.5
and 48, 1 and 72, 18 and 54, 30 and 42h (Figure 4H); 1
down-regulated gene at three time points (Figure 4H); 2
down-regulated genes at more time points (Figure 4H); 2
down-regulated genes at two time points/one phase (Figure
4I); 1 down-regulated gene at one phase, i.e. 6-12h (Figure
4I); 2 down-regulated genes at one time point/two phases
(Figure 4I); 2 down-regulated genes at two time points/
one phase (Figure 4I); 6 fi rst down- and then up-regulated
genes (Figure 4J); 4 first up- and then down-regulated
genes (Figure 4K); 8 up/down-regulated genes (Figure 4L).
DISCUSSION
Innate immune response, which is a self-protection
mechanism formed during the long-term evolutionary
process, includes tissue barrier, innate cellular immunity
and innate molecular immunity, being closely linked to
existence of high animal[2]. Of the proteins associated
with innate cellular immunity, seven proteins including
toll-like receptor 2 (TLR2) have a role in recognition
of pathogens, interferon excretion of NK cells and
activation of congenital immune system[24,25]; four proteins
including attractin (ATRN) positively regulate antigen
representation[26,27]; fifteen proteins including CCAAT/
Figure 3 Expression sim ilarity and tim e relevance clusters of 85 innate im m une response-associated genes during liver regeneration. Data detected by rat genom e 230
2.0 array were analyzed by H-clustering. Red indicates up-regulated gene expression chiefl y associated with cellular im m unity; green indicates down-regulated gene
expression m ainly associated with m olecular im m unity; black indicates m eaningless change in gene expression. The upper and right trees show the expression sim ilarity
and tim e series clusters, by which the above genes were classifi ed into 5 and 14 groups respectively.
96
16
42
30
68
44
20
72
24
18
48
60
54
66
1
0.5
4
8
6
2
36
12
0.6
0.5
0.4
0.3
0.2
0.1
0.0
-0.1
-0.2
-0.3
-0.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
-0.2
-0.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
-0.2
-0.4
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
-0.2
-0.4
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0.0
-0.5
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
-0.2
-0.4
0.4
0.3
0.2
0.1
0.0
-0.1
-0.2
-0.3
-0.4
-0.5
0.4
0.2
0.0
-0.2
-0.4
-0.6
-0.8
-1.0
0.4
0.2
0.0
-0.2
-0.4
-0.6
-0.8
-1.0
2.0
1.5
1.0
0.5
0.0
-0.5
-1.0
-1.5
2.0
1.5
1.0
0.5
0.0
-0.5
-1.0
1.5
1.0
0.5
0.0
-0.5
-1.0
-1.5
Figure 4 Expression patterns of 85 innate im m une response-associated genes during liver regeneration. Twenty-eight expression patterns were obtained by the analysis
of data detected by rat genom e 230 2.0 array with Microsoft Excel. A-F: 41 up-regulated genes; G-I: 26 down-regulated genes; J-L: 18 up/down-regulated genes. X-axis
represents recovery tim e after PH (h); Y-axis shows logarithm ratio of the signal values of genes at each tim e point to control.
A
B
C
D
E
FG
H
I
JK
L
1 4 8 16 24 36 48 60 72 120 168
1 4 8 16 24 36 48 60 72 120 168
1 4 8 16 24 36 48 60 72 120 168
1 4 8 16 24 36 48 60 72 120 168
1 4 8 16 24 36 48 60 72 120 168
1 4 8 16 24 36 48 60 72 120 1681 4 8 16 24 36 48 60 72 120 168
1 4 8 16 24 36 48 60 72 120 168
1 4 8 16 24 36 48 60 72 120 168
1 4 8 16 24 36 48 60 72 120 168
1 4 8 16 24 36 48 60 72 120 168
1 4 8 16 24 36 48 60 72 120 168
www.wjgnet.com
7856 ISSN 1007-9327 CN 14-1219/R World J Gastroenterol December 28, 2006 Volume 12 Number 48