Change in Annexin A3 Expression by Regulatory Factors of Hepatocyte Growth in Primary Cultured Rat Hepatocytes

Harashima, Mizuho; Niimi, Shingo; Koyanagi, H; Hyuga, Masashi; Noma, Seiji; Seki, Taiichiro; Ariga, Toshio; Kawanishi, Toru; Hayakawa, Tetsuo

doi:10.1248/bpb.29.1339

Cited by 15 publications

(13 citation statements)

References 36 publications

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“…Results are the average of two or three groups of data analyzed. Genes with an asterisk were not assigned to any GO category, but are known to be related to cell growth or apoptosis (34,35). …”

Section: Resultsmentioning

confidence: 99%

Identification of transcriptional regulatory cascades in retinoic acid-induced growth arrest of HepG2 cells

Nakanishi

Tomaru

Miura

et al. 2008

Nucleic Acids Research

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All-trans retinoic acid (ATRA) is a potent inducer of cell differentiation and growth arrest. Here, we investigated ATRA-induced regulatory cascades associated with growth arrest of the human hepatoma cell line HepG2. ATRA induced >2-fold changes in the expression of 402 genes including 55 linked to cell-cycle regulation, cell growth or apoptosis during 48 h treatment. Computational search predicted that 250 transcriptional regulatory factors (TRFs) could recognize the proximal upstream regions of any of the 55 genes. Expression of 61 TRF genes was significantly changed during ATRA incubation, providing many potential regulatory edges. We focused on six TRFs that could regulate many of the 55 genes and found a total of 160 potential edges in which the expression of each of the genes was changed later than the expression change of the corresponding regulator. RNAi knockdown of the selected TRFs caused perturbation of the respective potential targets. The genes showed an opposite regulation pattern by ATRA and specific siRNA treatments were selected as strong candidates for direct TRF targets. Finally, 36 transcriptional regulatory edges were validated by chromatin immunoprecipitation. These analyses enabled us to depict a part of the transcriptional regulatory cascades closely linked to ATRA-induced cell growth arrest.

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Section: Resultsmentioning

confidence: 99%

Identification of transcriptional regulatory cascades in retinoic acid-induced growth arrest of HepG2 cells

Nakanishi

Tomaru

Miura

et al. 2008

Nucleic Acids Research

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“…14 Furthermore, annexin A3 has been implicated as an angiogenic factor based upon its ability to induce tubule formation and migration of cultured human umbilical vein endothelial cells possibly through its ability to enhance transcription of hypoxia-induced factor 1 transcription factor. 17 Finally, annexin A3 proteins levels correlated with growth activity of rat hepatocytes 18 and decreased annexin A3 mRNA levels through the expression of interference RNA resulted in decreased hepatocyte cell division. 19 Based upon this diverse but potentially synergistic biochemical signaling, annexin A3 may be a key regulator of the neutrophil-endothelial cell microenvironment which is at the leading edge of vasculitic activity.…”

Section: Discussionmentioning

confidence: 98%

Leukocyte gene expression signatures in antineutrophil cytoplasmic autoantibody and lupus glomerulonephritis

Alcorta

Barnes²,

Dooley

et al. 2007

Kidney International

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Leukocytes play a major role in the development and progression of autoimmune diseases. We measured gene expression differences in leukocytes from patients that were antineutrophil cytoplasmic autoantibody (ANCA) positive, patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA), and healthy donors to explore potential pathways for clinical intervention. Leukocyte gene expression profiles were determined on Affymetrix U133A/B chips in 88 autoimmune patients, 28 healthy donors, and healthy donor leukocyte cell subtypes that were activated in vitro. Comparison of gene expression in leukocytes identified differentially expressed signature genes that distinguish each donor source. The microarray expression levels for many signature genes correlated with the clinical activity of small vessel vasculitis in the ANCA patients; a result confirmed by quantitative real time-polymerase chain reaction for 16 relevant genes. Comparison with in vitro-activated leukocyte subtypes from healthy donors revealed that the ANCA signature genes were expressed by neutrophils while the SLE signature genes were expressed in activated monocytes and T cells. We have found that leukocyte gene expression data can differentiate patients with RA, SLE, and ANCA-related small vessel vasculitis. Monitoring changes in the expression of specific genes may be a tool to help quantify disease activity during treatment.

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“…48 ANXA3 is involved in positive growth regulation of cultured rat hepatocytes and is one of the factors crucial for hepatocyte growth in culture. Harashima et al 49 observed a close correlation between stimulatory (hepatocyte growth factor and epidermal growth factor) and inhibitory (dexamethasone, subconfluent cell density) factors influencing hepatocyte growth and ANXA3 expression. We found both ANXA1 and ANXA3 among genes exclusively and differentially expressed in type 1 cells.…”

Section: Marker Genes Of Type 1 Progenitor Cellsmentioning

confidence: 97%

Molecular Characterization of Cultured Adult Human Liver Progenitor Cells

Józefczuk

Stachelscheid

Chávez

et al. 2010

Tissue Engineering Part C: Methods

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Hepatic progenitor cells hold great promise as a self-renewing cell source for cell-based regenerative therapies as well as in vitro pharmacological testing. There is a fundamental need to identify and characterize these cells with respect to discriminative marker genes especially those encoding cell surface proteins, which can be utilized for the identification and isolation of these progenitor cells. In this study, comparative global gene expression profiling was performed with two epithelial cell types isolated from human livers that showed progenitor characteristics (type 1 and 2 cells), two human embryonic stem cell lines H1 and H9, and with primary human hepatocytes. The analysis revealed that the transcriptome of type 1 cells is more similar to that of human embryonic stem cells than to that of human hepatocytes. Among the list of genes expressed in type 1 cells are cadherins (CDH3), tight junction proteins (CLDN4), receptors (DDR1), integrins (ITGB4), cell adhesion molecules (EpCAM/TACSTD1), cell surface proteins (CD133/PROM1, ANXA3, and CD24), and a gene encoding the multidrug resistance protein MRP4/ABCC4. Finally, we were able to localize type 1 progenitor cells in Canals of Hering and in cells of ductular reactions within sections of normal and diseased human liver using ANXA3 and CLDN4 antibodies. Our study confirms the progenitor identity of type 1 cells and identifies novel markers that could be used for further studies on their characteristics and isolation using marker-based cell sorting strategies.

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Change in Annexin A3 Expression by Regulatory Factors of Hepatocyte Growth in Primary Cultured Rat Hepatocytes

Cited by 15 publications

References 36 publications

Identification of transcriptional regulatory cascades in retinoic acid-induced growth arrest of HepG2 cells

Identification of transcriptional regulatory cascades in retinoic acid-induced growth arrest of HepG2 cells

Leukocyte gene expression signatures in antineutrophil cytoplasmic autoantibody and lupus glomerulonephritis

Molecular Characterization of Cultured Adult Human Liver Progenitor Cells

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