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Gene expression in the liver remnant is significantly affected by the size of partial hepatectomy : An experimental rat study. / Meier, Michelle; Knudsen, Anders Riegels; Andersen, Kasper Jarlhelt et al.
In: Gene Expression, Vol. 17, No. 4, 2017, p. 289-299.Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review
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TY - JOUR
T1 - Gene expression in the liver remnant is significantly affected by the size of partial hepatectomy
T2 - An experimental rat study
AU - Meier, Michelle
AU - Knudsen, Anders Riegels
AU - Andersen, Kasper Jarlhelt
AU - Bjerregaard, Niels Christian
AU - Jensen, Uffe Birk
AU - Mortensen, Frank Viborg
PY - 2017
Y1 - 2017
N2 - Extended hepatectomies may result in posthepatectomy liver failure, a condition with a high mortality. The main purpose of the present study was to investigate and compare the gene expression profiles in rats subjected to increasing size of partial hepatectomy (PH). Thirty Wistar rats were subjected to 30%, 70%, or 90% PH, sham operation, or no operation. Twenty-four hours following resection, liver tissue was harvested and genome-wide expression analysis was performed. Cluster analysis revealed two main groupings, one containing the PH(90%) and one containing the remaining groups [baseline, sham, PH(30%), and PH(70%)]. Categorization of specific affected molecular pathways in the PH(90%) group revealed a downregulation of cellular homeostatic function degradation and biosynthesis, whereas proliferation, cell growth, and cellular stress and injury were upregulated in the PH(90%) group. After PH(90%), the main upregulated pathways were mTOR and ILK. The main activated upstream regulators were hepatocyte growth factor and transforming growth factor. With decreasing size of the future liver remnant, the liver tended to prioritize expression of genes involved in cell proliferation and differentiation at the expense of genes involved in metabolism and body homeostasis. This prioritizing may be an essential molecular explanation for posthepatectomy liver failure.
AB - Extended hepatectomies may result in posthepatectomy liver failure, a condition with a high mortality. The main purpose of the present study was to investigate and compare the gene expression profiles in rats subjected to increasing size of partial hepatectomy (PH). Thirty Wistar rats were subjected to 30%, 70%, or 90% PH, sham operation, or no operation. Twenty-four hours following resection, liver tissue was harvested and genome-wide expression analysis was performed. Cluster analysis revealed two main groupings, one containing the PH(90%) and one containing the remaining groups [baseline, sham, PH(30%), and PH(70%)]. Categorization of specific affected molecular pathways in the PH(90%) group revealed a downregulation of cellular homeostatic function degradation and biosynthesis, whereas proliferation, cell growth, and cellular stress and injury were upregulated in the PH(90%) group. After PH(90%), the main upregulated pathways were mTOR and ILK. The main activated upstream regulators were hepatocyte growth factor and transforming growth factor. With decreasing size of the future liver remnant, the liver tended to prioritize expression of genes involved in cell proliferation and differentiation at the expense of genes involved in metabolism and body homeostasis. This prioritizing may be an essential molecular explanation for posthepatectomy liver failure.
KW - Gene expression
KW - Hepatectomy
KW - Liver failure
KW - Microarray analysis
KW - Regeneration
UR - http://www.scopus.com/inward/record.url?scp=85035777357&partnerID=8YFLogxK
U2 - 10.3727/105221617X695825
DO - 10.3727/105221617X695825
M3 - Journal article
C2 - 28488569
AN - SCOPUS:85035777357
VL - 17
SP - 289
EP - 299
JO - Gene Expression Patterns
JF - Gene Expression Patterns
SN - 1567-133X
IS - 4
ER -