ANALYZING THE REGULATING GENES OF LIVER REGENERATION IN CHANGING DEGREE, PATTERN, TIMING AND VERIFYING THE ROLES OF SPECIFIC AND CLUSTER GENES BY cDNA MICROARRY (2/2)
Date Issued
2005-07-31
Date
2005-07-31
Author(s)
賴鴻緒
DOI
932314B002056
Abstract
Although there are much controversy
on the initiation, regulation, metabolic
changes, and termination of liver
regeneration after partial hepatectomy that
well initiate proliferation of the remaining
hepatocytes, several factors, such as
hormones, growth factors, nutritional
components, and pharmacological agents,
have been demonstrated to directly or
indirectly affect liver regeneration.
However, the regenerative mechanism and
genetic control of liver after major tissue loss
is still not clear.
We used 70% portal hepatectomized rat
model for studying genes variation after
partial hepatectomy, and found that: (1) the
remnant liver weight increased to 90% in 72h
after partial hepatectomy; (2) the mitosis of
hepatocytes increased marked at 48h then
decreased at 72h after partial hepatectomy; (3)
analyzing the gene expression of microarray
chips, the variation could be classified into
72 different patterns in cluding the patterns
with a single peak at 2, 4, 6, 12, 24, 72h and
5, 7d after partial hepatectomy; (4) gene
clusters of immune, hormone, growth factor,
enzyme and angiogenesis have changed
markedly; (5) early stage changed genes
including fas-associating protein with death
domain, carnitine palmitoyltransferase 1, fas
death domain-associating protein, and steroid
O-acyltransferase 1 could be related to the
initiation of liver regeneration; (6)
intermediate stage changed genes including
transforming growth factor beta 2 and beta
receptor could be related to the
differentiation of liver regeneration; (7) late
stage changed genes including TGF-β
regulated gene 3 and small inducible
cytokine A2 could be related to the
termination of liver regeneration. Study with
40% partial hepatectomy was performed in
the second year.
Male Wistar rats around 200g will be
used as subject. Partial hepatectomy around
40% were performed. They were sacrificed
before and 2, 4, 6, 12, 24, 72 hours and 5, 7,
10 days after hepatectomy. We have
measured: (1)weight of remnant liver;
(2)mitotic index; (3)genomic survey of the
gene expression by microarray chip of
20,500 identified cDNA clones, labeling of
liver mRNA hybridization and image
analysis; and (4)Grouping of genes
expression into immune, nutrition, hormone,
growth factor, enzyme, oncologic and
embryonic subgroups, and compare the
expression degree, changing pattern and
specific timing.
The results were: (1) the remnant liver
weight recovered slower, but can reach 90%
in 72h after partial hepatectomy; (2) the
mitosis of hepatocytes also increased
markedly at 48h although not so high as 70%
group rats, and also decreased at 72h after
partial hepatectomy; (3) analyzing the gene
expression of microarray chips, the variation
of 40% group rats could also be classified
into 72 patterns just like 70% group, with
some variation degree were not so marked as
70% group rats; (4) gene clusters of immune,
hormone, growth factor, enzyme and
angiogenesis have changed markedly; (5)
The changes of gene expression in immune
related genes (such as IL-6 and IL-10 control
genes) and angiogenesis related genes (such
as Angiotensiongen, VEGF, and VEGF-receptor 2) were more similar to the
remnant liver weight variations. It may
indicate that these genes play more important
roles in the control mechanism of liver
regeneration.
Subjects
liver regeneration
partial
hepatectomy
hepatectomy
microarray
genetic changing pattern
gene cluster
Publisher
臺北市：國立臺灣大學醫學院外科
Type
report
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