Inhibited activities in CCAAT/enhancer-binding protein, activating protein-1 and cyclins after hepatectomy in rats with thioacetamide-induced liver cirrhosis

Gang Zhao, Kenji Nakano, Kazuo Chijiiwa, Junji Ueda, Masao Tanaka

    Research output: Contribution to journalArticle

    17 Citations (Scopus)

    Abstract

    Transcriptional activation of nuclear factor (NF)-κB, signal transducers and activators of transcription (STAT) 3, activating protein (AP)-1 and CCAAT/enhancer-binding protein (C/EBP) plays an important role in liver regeneration by modulating cell cycle regulators. The regeneration of cirrhotic liver after hepatectomy is inhibited despite intact expression of growth factors. To elucidate the mechanism involved, regeneration responses in growth factor receptors, transcription factors, and cell cycle regulators after two-thirds hepatectomy were compared between rats with thioacetamide-induced cirrhotic and normal liver. The expression of c-met and epidermal growth factor receptor analyzed by RT-PCR and immunohistochemistry did not differ between the two groups. The activities of C/EBP and AP-1 evaluated by electrophoretic mobility shift assay were significantly inhibited in the cirrhotic group compared with those in the control group, but not those of NF-κB and STAT3. The expression of cyclin-D1, -E, and -A assessed by Western blot analysis was significantly decreased in the cirrhotic group compared with the control group. The level in p21Cip1 or p27Kip1 did not differ between the two groups. The liver regeneration estimated by the rates of [3H]thymidine incorporation into DNA and staining of proliferating cell nuclear antigen was significantly lower in the cirrhotic rats than in the controls. In conclusion, downregulation of cyclin -D1, -E, and -A expression, which may be induced by impaired activities of C/EBP and AP-1, is responsible for the decreased regenerative capacity of cirrhotic liver after partial hepatectomy.

    Original languageEnglish
    Pages (from-to)474-481
    Number of pages8
    JournalBiochemical and Biophysical Research Communications
    Volume292
    Issue number2
    DOIs
    Publication statusPublished - Mar 29 2002

    Fingerprint

    Thioacetamide
    CCAAT-Enhancer-Binding Proteins
    Liver Regeneration
    Cyclins
    Hepatectomy
    Liver Cirrhosis
    Liver
    Rats
    Cyclin E
    Cyclin D1
    Cell Cycle
    STAT3 Transcription Factor
    Control Groups
    Proteins
    Growth Factor Receptors
    Proliferating Cell Nuclear Antigen
    Electrophoretic Mobility Shift Assay
    Epidermal Growth Factor Receptor
    Thymidine
    Transcriptional Activation

    All Science Journal Classification (ASJC) codes

    • Biophysics
    • Biochemistry
    • Molecular Biology
    • Cell Biology

    Cite this

    Inhibited activities in CCAAT/enhancer-binding protein, activating protein-1 and cyclins after hepatectomy in rats with thioacetamide-induced liver cirrhosis. / Zhao, Gang; Nakano, Kenji; Chijiiwa, Kazuo; Ueda, Junji; Tanaka, Masao.

    In: Biochemical and Biophysical Research Communications, Vol. 292, No. 2, 29.03.2002, p. 474-481.

    Research output: Contribution to journalArticle

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    abstract = "Transcriptional activation of nuclear factor (NF)-κB, signal transducers and activators of transcription (STAT) 3, activating protein (AP)-1 and CCAAT/enhancer-binding protein (C/EBP) plays an important role in liver regeneration by modulating cell cycle regulators. The regeneration of cirrhotic liver after hepatectomy is inhibited despite intact expression of growth factors. To elucidate the mechanism involved, regeneration responses in growth factor receptors, transcription factors, and cell cycle regulators after two-thirds hepatectomy were compared between rats with thioacetamide-induced cirrhotic and normal liver. The expression of c-met and epidermal growth factor receptor analyzed by RT-PCR and immunohistochemistry did not differ between the two groups. The activities of C/EBP and AP-1 evaluated by electrophoretic mobility shift assay were significantly inhibited in the cirrhotic group compared with those in the control group, but not those of NF-κB and STAT3. The expression of cyclin-D1, -E, and -A assessed by Western blot analysis was significantly decreased in the cirrhotic group compared with the control group. The level in p21Cip1 or p27Kip1 did not differ between the two groups. The liver regeneration estimated by the rates of [3H]thymidine incorporation into DNA and staining of proliferating cell nuclear antigen was significantly lower in the cirrhotic rats than in the controls. In conclusion, downregulation of cyclin -D1, -E, and -A expression, which may be induced by impaired activities of C/EBP and AP-1, is responsible for the decreased regenerative capacity of cirrhotic liver after partial hepatectomy.",
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