AIM: To investigate the role of genes and kinetics of specific transcription factors in liver regeneration, and to analyze the gene expression and the activity of some molecules crucially involved in hepatic regenerat...AIM: To investigate the role of genes and kinetics of specific transcription factors in liver regeneration, and to analyze the gene expression and the activity of some molecules crucially involved in hepatic regeneration. METHODS: USING gel-shift assay and RT-PCR, transcription factors, such as NF-κB, STAT-3, SMAD3 and AP-1, and gene expression of inducible nitric oxide synthase (iNOS), hepatocyte growth factor (HGF) and c-met were analyzed in an animal model of chemically induced hepatectomy. RESULTS: Gene expression of HGF and its receptor c-met peaked at 3 h and 24 h after acute CCl4 intoxi- cation. iNOS expression was only observed from 6 to 48 h. Transcriptional factor NF-κB had an early activation at 30 min after acute liver damage. STAT-3 peaked 3 h post- intoxication, while AP-1 displayed a peak of activation at 48 h. SMAD3 showed a high activity at all analyzed times. CONCLUSION: TNF-α and IL-6 play a central role in hepatic regeneration. These two molecules are responsible for triggering the cascade of events and switch-on of genes involved in cell proliferation, such as growth factors, kinases and cyclins which are direct participants of cell proliferation.展开更多
AIM: To study the distribution pattern of transcription factors NF-kB and AP-1 and their relations with the expression of apoptosis associated-proteins Fas/FasL and ICH-1L/S in human hepatocellular carcinoma (HCC). ME...AIM: To study the distribution pattern of transcription factors NF-kB and AP-1 and their relations with the expression of apoptosis associated-proteins Fas/FasL and ICH-1L/S in human hepatocellular carcinoma (HCC). METHODS: We performed in situ hybridization and immunohistochemical techniques for NF-kB, AP-1, Fas/FasL and ICH-1 in 40 cases of human HCC along with corresponding nontumoral tissues and 7 cases of normal liver tissues. RESULTS: Twenty-two (55%) and 25 (62.5%) of 40 cases for NF-κB and AP-1 were presented for nuclear or both nuclear and cytoplastic staining respectively, while less cases were presented for only cytoplastic staining for NF-κB (18%) and AP-1 (10%) in adjacent nontumoral tissues and negative staining in normal liver tissues. There was no statistically significant difference of NF-κB or AP-1 activation between well differentiated tumors and poorly differentiated tumors (P>0.05). NF-κkB activity is positively corresponded to AP-1 activation. The expression of ICH-1L/S was associated with the activation of NF-κB and AP-1 (P<0.05), but no significant relationship was found between Fas/FasL and NF-κB or AP-l(P>0.05). CONCLUSION: Activation of both NF-κB and AP-1 may be required for ICH-1L/S-induced apoptosis in HCC, but not for Fas/FasL-mediated apoptosis. NF-κB and AP-1 may play important roles in the pathogenesis of human HCC.展开更多
基金Supported by CONACyT grant # 28827-M to Adriana Salazar-Montes and, in part, by COECyTJal grant # 08-2004 to Juan Armendariz-Borunda
文摘AIM: To investigate the role of genes and kinetics of specific transcription factors in liver regeneration, and to analyze the gene expression and the activity of some molecules crucially involved in hepatic regeneration. METHODS: USING gel-shift assay and RT-PCR, transcription factors, such as NF-κB, STAT-3, SMAD3 and AP-1, and gene expression of inducible nitric oxide synthase (iNOS), hepatocyte growth factor (HGF) and c-met were analyzed in an animal model of chemically induced hepatectomy. RESULTS: Gene expression of HGF and its receptor c-met peaked at 3 h and 24 h after acute CCl4 intoxi- cation. iNOS expression was only observed from 6 to 48 h. Transcriptional factor NF-κB had an early activation at 30 min after acute liver damage. STAT-3 peaked 3 h post- intoxication, while AP-1 displayed a peak of activation at 48 h. SMAD3 showed a high activity at all analyzed times. CONCLUSION: TNF-α and IL-6 play a central role in hepatic regeneration. These two molecules are responsible for triggering the cascade of events and switch-on of genes involved in cell proliferation, such as growth factors, kinases and cyclins which are direct participants of cell proliferation.
文摘AIM: To study the distribution pattern of transcription factors NF-kB and AP-1 and their relations with the expression of apoptosis associated-proteins Fas/FasL and ICH-1L/S in human hepatocellular carcinoma (HCC). METHODS: We performed in situ hybridization and immunohistochemical techniques for NF-kB, AP-1, Fas/FasL and ICH-1 in 40 cases of human HCC along with corresponding nontumoral tissues and 7 cases of normal liver tissues. RESULTS: Twenty-two (55%) and 25 (62.5%) of 40 cases for NF-κB and AP-1 were presented for nuclear or both nuclear and cytoplastic staining respectively, while less cases were presented for only cytoplastic staining for NF-κB (18%) and AP-1 (10%) in adjacent nontumoral tissues and negative staining in normal liver tissues. There was no statistically significant difference of NF-κB or AP-1 activation between well differentiated tumors and poorly differentiated tumors (P>0.05). NF-κkB activity is positively corresponded to AP-1 activation. The expression of ICH-1L/S was associated with the activation of NF-κB and AP-1 (P<0.05), but no significant relationship was found between Fas/FasL and NF-κB or AP-l(P>0.05). CONCLUSION: Activation of both NF-κB and AP-1 may be required for ICH-1L/S-induced apoptosis in HCC, but not for Fas/FasL-mediated apoptosis. NF-κB and AP-1 may play important roles in the pathogenesis of human HCC.
