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Title: Identification of homeobox genes expressed during the process of rat liver regeneration after partial hapatectomy

Abstract

Homeobox (HBox) genes are well-known to be involved in development and differentiation. To ascertain a role of HBox genes in the process of liver regeneration, we identified HBox genes expressed at various times after partial hepatectomy in rats (at 0 hr, 1 hr, 2 days, and 4 days) by using reverse transcription-polymerase chain reaction (RT-PCR), cloning, and sequencing techniques. By the competitive RT-PCR method using generic primers, expression levels of HBox genes in regenerating livers were estimated at as low as only 0.4-2% of that in 14-day embryonic liver; however, we identified multiple HBox genes at different stages. Comparing sets of HBox genes identified at different stages, we could find two candidates of stage specifically expressed HBox genes (one rat caudal-related gene, RCdx-3, stimulated at 1 hr, and one rat Hox gene, RHoxB5, repressed after hepatectomy) and continuous expression of five Hox genes (RHoxAl, A4, A5, B2, and B3) before and after hepatectomy. These HBox genes are considered to correlate with the process of liver regeneration. 36 refs., 6 figs., 2 tabs.

Authors:
; ; ;  [1]
  1. Osaka Univ. (Japan)
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
273483
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical Genetics; Journal Volume: 34; Journal Issue: 1-2; Other Information: PBD: Feb 1996
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; GENES; DNA SEQUENCING; DNA-CLONING; GENE REGULATION; AMINO ACID SEQUENCE; ONTOGENESIS; LIVER; BIOLOGICAL REGENERATION; RATS; POLYMERASE CHAIN REACTION; NUCLEOTIDES; ELECTROPHORESIS

Citation Formats

Mizuta, Ikuko, Ogasawara, Naotake, Yoshikawa, Hiroshi, and Sakoyama, Yasuhiko. Identification of homeobox genes expressed during the process of rat liver regeneration after partial hapatectomy. United States: N. p., 1996. Web. doi:10.1007/BF02396236.
Mizuta, Ikuko, Ogasawara, Naotake, Yoshikawa, Hiroshi, & Sakoyama, Yasuhiko. Identification of homeobox genes expressed during the process of rat liver regeneration after partial hapatectomy. United States. doi:10.1007/BF02396236.
Mizuta, Ikuko, Ogasawara, Naotake, Yoshikawa, Hiroshi, and Sakoyama, Yasuhiko. 1996. "Identification of homeobox genes expressed during the process of rat liver regeneration after partial hapatectomy". United States. doi:10.1007/BF02396236.
@article{osti_273483,
title = {Identification of homeobox genes expressed during the process of rat liver regeneration after partial hapatectomy},
author = {Mizuta, Ikuko and Ogasawara, Naotake and Yoshikawa, Hiroshi and Sakoyama, Yasuhiko},
abstractNote = {Homeobox (HBox) genes are well-known to be involved in development and differentiation. To ascertain a role of HBox genes in the process of liver regeneration, we identified HBox genes expressed at various times after partial hepatectomy in rats (at 0 hr, 1 hr, 2 days, and 4 days) by using reverse transcription-polymerase chain reaction (RT-PCR), cloning, and sequencing techniques. By the competitive RT-PCR method using generic primers, expression levels of HBox genes in regenerating livers were estimated at as low as only 0.4-2% of that in 14-day embryonic liver; however, we identified multiple HBox genes at different stages. Comparing sets of HBox genes identified at different stages, we could find two candidates of stage specifically expressed HBox genes (one rat caudal-related gene, RCdx-3, stimulated at 1 hr, and one rat Hox gene, RHoxB5, repressed after hepatectomy) and continuous expression of five Hox genes (RHoxAl, A4, A5, B2, and B3) before and after hepatectomy. These HBox genes are considered to correlate with the process of liver regeneration. 36 refs., 6 figs., 2 tabs.},
doi = {10.1007/BF02396236},
journal = {Biochemical Genetics},
number = 1-2,
volume = 34,
place = {United States},
year = 1996,
month = 2
}
  • The polymerase chain reaction with degenerate primers corresponding to the most conservative amino acids 16-21 (ELEKEF) and 49-54 (WPQNRR) of the Antennapedia class homeodomains was used for the amplification of cDNA from regenerating planarians (asexual race of Dugesia tigrina). A total of six new Antennapedia-like homeobox sequences, designated Dutarh-1-Dutarh-6 (Dugesia tigrina asexual race homeobox gene), have been identified. Their comparison with other homeobox genes using a Genebee software (the EMBL Data Library) showed that all sequences except Dutarh-6 belong to the Antennapedia class. Dutarh-6 is closely related to a recently described novel homeobox gene subfamily which includes mouse mesodermal homeoboxmore » genes Max-1 and Max-2 and rat homeobox gene Gax. 17 refs., 2 figs.« less
  • Highlights: {yields} Hepatic steatosis in rats fed a high fructose diet was less severe than that in rats fed a high fat diet. {yields} Liver regeneration was more impaired in rats fed a high fructose diet than in rats fed a high fat diet. {yields} Dysregulation of genes associated with metabolism may contribute to impairment of liver regeneration. {yields} Regulation of the TGF-{beta}1 level after partial hepatectomy may be impaired in rats fed a high fructose diet. -- Abstract: Hepatic steatosis (HS) has a negative effect on liver regeneration, but different pathophysiologies of HS may lead to different outcomes. Malemore » Sprague-Dawley rats were fed a high fructose (66% fructose; H-fruc), high fat (54% fat; H-fat), or control chow diet for 4 weeks. Based on hepatic triglyceride content and oil red O staining, HS developed in the H-fruc group, but was less severe compared to the H-fat group. Hepatic mRNA expression levels of fatty acid synthase and fructokinase were increased and those of carnitine palmitoyltransferase-1 and peroxisome proliferator-activated receptor-{alpha} were decreased in the H-fruc group compared to the H-fat group. Liver regeneration after 70% partial hepatectomy (PHx) was evaluated by measuring the increase in postoperative liver mass and PCNA-positive hepatocytes, and was impaired in the H-fruc group compared to the H-fat and control groups on days 3 and 7. Serum levels of tumor necrosis factor-{alpha}, interleukin-6 and hepatocyte growth factor did not change significantly after PHx. In contrast, serum TGF-{beta}1 levels were slightly but significantly lower in the control group on day 1 and in the H-fat group on day 3 compared to the level in each group on day 0, and then gradually increased. However, the serum TGF-{beta}1 level did not change after PHx in the H-fruc group. These results indicate that impairment of liver regeneration after PHx in HS is related to the cause, rather than the degree, of steatosis. This difference may result from altered metabolic gene expression profiles and potential dysregulation of TGF-{beta}1 expression.« less
  • During liver regeneration induced by CCl/sub 4/ administration to rats, changes in the relative transcription rates of albumin and alpha-fetoprotein genes have been measured in conjunction with other liver-specific and general cellular function genes. Within 24 h following CCl/sub 4/ administration, albumin gene transcription decreases by 85%, whereas alpha-fetoprotein transcription increases from undetectable levels to 50% of that observed for albumin. These changes precede maximal (/sup 3/H)thymidine incorporation into DNA which peaks at 48 h. Other genes related to liver-specific functions, such as ligandin, alpha 1-antitrypsin, and cytochrome P-450's, as well as general cellular genes pro alpha 1- and promore » alpha 2-collagen, beta-actin, and alpha-tubulin, respond in kinetic patterns often distinct from each other and from albumin and alpha-fetoprotein. Changes in the steady-state levels of albumin and alpha-fetoprotein mRNA correlate with changes in transcription, but there is a lag in alpha-fetoprotein mRNA accumulation, which peaks at 72 h following CCl/sub 4/ administration. These studies indicate that reciprocal changes in albumin and alpha-fetoprotein gene transcription occur during CCl/sub 4/-induced liver regeneration, leading to changes in the level of these specific mRNAs. These changes precede DNA synthesis and would appear to represent an alteration in differentiated function of hepatocytes in conjunction with the liver regenerative process.« less
  • We previously demonstrated that adiponectin has anti-fibrogenic and anti-inflammatory effects in the liver of mouse models of various liver diseases. However, its role in liver regeneration remains unclear. The aim of this study was to determine the role of adiponectin in liver regeneration. We assessed liver regeneration after partial hepatectomy in wild-type (WT) and adiponectin knockout (KO) mice. We analyzed DNA replication and various signaling pathways involved in cell proliferation and metabolism. Adiponectin KO mice exhibited delayed DNA replication and increased lipid accumulation in the regenerating liver. The expression levels of peroxisome proliferator-activated receptor (PPAR) {alpha} and carnitine palmitoyltransferase-1 (CPT-1),more » a key enzyme in mitochondrial fatty acid oxidation, were decreased in adiponectin KO mice, suggesting possible contribution of altered fat metabolism to these phenomena. Collectively, the present results highlight a new role for adiponectin in the process of liver regeneration.« less
  • Purpose: To analyze the influence of the adjuvant radiotherapy (RT) on the liver regeneration and liver function after partial hepatectomy (PH). Methods and Materials: Thirty-four patients who underwent PH for biliary tract cancer between October 2003 and July 2005 were reviewed. Hemihepatectomy was performed in 14 patients and less extensive surgery in 20. Of the patients, 19 patients had no adjuvant therapy (non-RT group) and 15 underwent adjuvant RT by a three-dimensional conformal technique (RT group). Radiation dose range was 40 to 50 Gy (median, 40 Gy). Liver volume on computed tomography and the results of liver function tests atmore » 1, 4, 12, 24, and 52 weeks after PH were compared between the RT and non-RT groups. Results: The preoperative characteristics were identical for both groups. During the interval between Weeks 4 and 12 when adjuvant RT was delivered in the RT group, the increase in liver volume was significantly smaller in the RT group than non-RT group (22.9 {+-} 38.3cm{sup 3} and 81.5 {+-} 75.6cm{sup 3}, respectively, p = 0.007). However, the final liver volume measured at 1 year after PH did not differ between the two groups (p = 0.878). Liver function tests were comparable for both groups. The resection extent and original liver volume was independent factors for final liver volume measured at 1 year after PH. Conclusions: In this study, adjuvant RT delayed the liver regeneration process after PH, but the volume difference between the two study groups became nonsignificant after 1 year. Adjuvant RT had no additional adverse effect on liver function after PH.« less