BACKGROUND : c-fos and c-jun, the important immediate early genes (IEG), are regarded as the markers for the location and function of neuronal activity, as well as the third signal messengers, they couple the stres...BACKGROUND : c-fos and c-jun, the important immediate early genes (IEG), are regarded as the markers for the location and function of neuronal activity, as well as the third signal messengers, they couple the stress stimulation and the gene expression in neuron, and hippocampus is involved in the process of signal transmission after stress stimulation induced depression. OBJECTIVE: To observe the therapeutic effects of Bushen Yiqi (tonifying kidney to benefit qi), Huoxue Huayu (promoting blood circulation to dissipate blood stasis) and Ditan Kaiqiao (eliminating phlegm for resuscitation) on the expressions of c-Fos and c-Jun proteins in hippocampus and spontaneous behaviors of rats with post-stroke depression (PSD), and compare the results with those of fluoxetine, which is known to have definite effect on depression. DESIGN: A randomized controlled tna SETTING : Zhejiang College of Traditional Chinese Medicine MATERIALS : The trial was completed in Zhejiang College of Traditional Chinese Medicine from January to July in 2003. Fifty-six healthy adult Wistar male rats of clean grade, weighing (250±50) g, were randomly divided into 7 groups with 8 rats in each group: control group, model group, forced swimming group, Bushen Yiqi group; Huoxue Huayu, Ditan Kaiqiao group and fluoxetine group. The Bushen Yiqi Tang contained Renshen, Huangqi, Heshouwu, Gouqi, Shudi, etc., crude drugs 1 800 g/L. The Huoxue Huayu Tang contained Danshen, Chuanxiong, Chishao, Yujin, etc., crude drugs 3 600 g/L. The Ditan Kaiqiao Tang contained Banxia, Danxing, Changpu, Yuanzhi, etc., crude drug 1 000 g/b METHODS: ① Except the control group and forced swimming group, rats in the other groups were made into PSD models by deligating the bilateral common carotid artedes permanently. ② Rats in the control group, model group and forced swimming group were intragastncally perfused by saline (3 mL for each time); those in the Bushen Yiqi group, Huoxue Huayu, Ditan Kaiqiao group and fluoxetine group were intragastncally perfused with Bushen Yiqi Tang (18 g/kg), Huoxue Huayu Tang (9 g/kg), Ditan Kaiqiao Tang (9 g/kg) and fluoxetine (2.5 mg/kg) respectively, once a day. ③ At 55 days after model establishment, rats in the forced swimming group were managed according to the Porsolt's method. They were placed in water for 15 minutes, and then taken out and dned, no moving-time within 5 minutes was recorded at drying and 24 hours after drying. ④ Measurement of spontaneous behaviors: Except the forced swimming group, the spontaneous behaviors and activities (including horizontal and vertical movements) of rats were observed with the Open-Field method at 28, 42 and 56 days after administration in the other groups. ⑤ The expressions of c-Fos and coJun proteins in hippocampus were determined with the immunohistochemical method, the relative sectional area ratio and average objective gray value of c-Fos and c-Jun positive cells in hip- pocampus were measured with the computerized image analytical system. MAIN OUTCOME MEASURES: The spontaneous behaviors of rats, the relative sectional area ratio and average objective gray value of c-Fos and c-Jun positive cells in hippocampus were observed. RESULTS: Of the 56 rats, 1 died in the forced swimming group, and finally 55 rats were involved in the analysis of results. ① Results of spontaneous activities: At 28 days, the times of crossing movements were obviously fewer in the model group and fluoxetine group [(69.00±37.01), (98.11 ±36.68) times/3 minutes] than in the control group [(128.44±16.85) times/3 minutes, P 〈 0.01, 0.05], but those in the Bushen Yiqi group, Huoxue Quyu group and Ditan Kaiqiao group had no obvious differences as compared with those in the control group (P 〉 0.05). At 42 and 56 days, the times of crossing movements were obviously more in the Bushen Yiqi group, Huoxue Quyu group and Ditan Kaiqiao group [(106.44±31.24), (117.20±23.95), (134.80±28.18), (136.36±40.95) times/3 minutes; (117.33±35.91), (129.60 ±23.78), (131.90 ±26.81), (136.09±28.34) times/3 minutes] than in the model group [(64.00±17.51), (72.86±20.68) times/3 minutes, P 〈 0.01]. The times of rearing movements had no obvious differences among the groups for the three times (P 〉 0.05). ② The no moving-time within 5 minutes 24 hours after drying was obviously longer than that at drying in the forced swimming group. ③ The average objective gray values of c-Fos positive cells were not obviously different in the Bushen Yiqi group and Ditan Kaiqiao group from the control group (P 〉 0.05), but lower in the model group than in the control group (69.84±9.82, 75.78±5.89, P 〈 0.01), and higher in the forced swimming group than in the control group (85.97±10.99, P 〈 0.01); all higher in the fluoxetine group, Bushen Yiqi group, Huoxue Quyu group and Ditan Kaiqiao group than in the model group (81.27±10.73, 74.04±8.34, 83.29±9.89, 70.14±4.92, P 〈 0.05-0.01). The average objective gray values of c-Jun positive cells were obviously lower in the Bushen Yiqi group than in the control group (68.11 ±6.89, 79.58±5.86, P 〈 0.01), but all higher in the other groups than in the control group (84.68±7.15, 81.34 ±8.36, 97.51±10.55, 85.68±9.25, 86.19±10.98, P 〈 0.05-0.01); Those were obviously higher in the fluoxetine group, Huoxue Quyu group and Ditan Kaiqiao group than in the model group (P 〈 0.05-0.01 ), lower in the Bushen Yiqi group than in the model group (P 〈 0.05), all obviously lower in the Bushen Yiqi group, Huoxue Quyu group and Ditan Kaiqiao group than in the fluoxetine group (P 〈 0.01). The relative sectional area ratios of c-Fos and c-Jun positive cells had no obvious differences among the groups (P 〉 0.05). CONCLUSION : The methods of Bushen Yiqi, Huoxue Quyu and Ditan Kaiqiao can effectively treat PSD in rats, and the results were equivalent with those of fluoxetine, the actions of the above-mentioned drugs may correlated with their regulation to c-Fos and c-Jun expressions in hippocampus. PSD animal models can be successfully established by both permanent deligation of bilateral common carotid arteries and forced swimming, and the models induced by the former has similar basic cerebrovascular lesions as human stroke in clinic.展开更多
Objective:To investigate the expression and significance of the MMP-7,c-Jun and c-Fos in rat photoaging skin.Methods:A total of 45 SD rats were randomly divided into control group,model group,natural recovery group,ph...Objective:To investigate the expression and significance of the MMP-7,c-Jun and c-Fos in rat photoaging skin.Methods:A total of 45 SD rats were randomly divided into control group,model group,natural recovery group,physiological saline injection group and dermal pluripotent stem cells transplantation(DMSCs group),model group,natural recovery group,physiological saline injection group.DMSCs were treated with UV lamp irradiation to establish light aging skin model.Rats were then sacrificed after model prepared,no treatment was processed in the natural recovery group.Saline injections was adopted in saline group,DESCs group was treated with DESCs transplantation.Rats were sacrificed after 4 weeks.The expression of MMP-7,c-Jun and c-Kos were detected using the immunohistocheniical metluxl.Results:In model group,MMP 7positive expression was higher than that in the other 4 groups,but without statistically difference(P>0.05);c-Jun,c-Fos expression were higher than that in the control group and DESCs group(P<0.05),there was no significant difference comparing natural recovery group with physiological saline injection group(P>0.05).Conclusions:MMP-7,c-Jun and c-Fos can be used as diagnosis indicators in the early stage of light aging,and they jointly participate in its development.DMSCs transplants is effective in treating light aging skin.展开更多
BACKGROUND: Both c-Fos protein and nitricoxide synthase (NOS) have been used as general indexes in relative research about neurons, but it is lack of reports that c-Fos protein and NOS are applied synchronously to ...BACKGROUND: Both c-Fos protein and nitricoxide synthase (NOS) have been used as general indexes in relative research about neurons, but it is lack of reports that c-Fos protein and NOS are applied synchronously to study the neurons of hypoxic fetal rats in uterus. OBJECTIVE: To study the effect of hypoxia in uterus on the expression of c-Fos protein and NOS in neurons of cerebral cortex from fetal rats and whether Angelica sinensis has the protective effect on these neurons in hypoxia. DESIGN: Randomized control experiment.SETTING : Department of Histology and Embryology, Luzhou Medical College.MATERIALS : Twelve adult female Wistar rats in oestrum and 1 male Wistar rat with bodymass from 220 to 250 g were chosen. Parenteral solution of Angelica sinensis mainly contained angelica sinensis, 10 mL/ampoule, was provided by Department of Agent of the Second Hospital Affiliated to Hubei Medical University (batch number: 01062310). METHODS : This experiment was completed in the Department of Histology and Embryology of Luzhou Medical College from September 2003 to June 2004. ①Twelve adult female Wistar rats in oestrum and 1 male Wistar rat were housed in one rearing cage. Vaginal embolus was performed on conceive female rat at 8: 00 am next day. On the 15^th conceiving day, all conceiving rats were divided randomly into three groups: control group, hypoxia group and Angelica group with 4 in each group. Rats in hypoxia group and Angelica group were modeled with hypotonic hypoxia in uterus. Angelica group: Rats were injected with 8 mL/kg Angelica sinensis injection through caudal veins before hypoxia. Hypoxia group: Rats were injected with the same volume of saline. Control group: Rats were not modeled and fed with normal way. ② Twenty embryos of rats were chosen randomly from each group and then routinely embedded in paraffin. Paraffin sections were cut from the brain of embryos to anterior fontanelle. Double-label staining was used to detect the expression of nNOS and c-Fos in neurons of cerebral cortex from embryos of rats. OLYMPUS Bx-50 microscope was used to observe sections and DP12 digit camera was also used under 400 times to detect types of cells. Under microscope, the number of c-Fos, NOS, c-Fos/NOS positive neurons in cerebral cortex from embryos of rats were counted in 2 fields with magnification of 400 in one section per animal. ③ The data in experiments were analyzed by one-way analysis of variance (ANOVA) followed by q test. MAIN OUTCOME MEASURES: ① Results of immunohistochemical double-label staining of c-Fos/NOS from cerebral cortex; ② Comparison of amount immunohistochemical double-label staining of c-Fos/NOS positive cells from cerebral cortex. RESULTS:① The positive NOS cells and c-Fos/NOS cells in the three groups were mainly distributed in cerebral cortex, but positive c-Fos neurons were not observed. ② Positive NOS cells and c-Fos/NOS cells in hypoxia group were more than those in control group (76.55±12.02, 50.45±10.39; 33.35±7.42, 26.35±6.67, P 〈 0.05), but those in Angelica group were less than those in hypoxia group (51.70±9.82, 35.65±8.37, P 〈 0.05). CONCLUSION: Hypoxia can stimulate the increase of expression of c-Fos protein and NOS in neurons of cerebral cortex. However, Angelica sinensis can decrease this expression so as to play a protective role in cerebral neurons of hypoxic fetal rats.展开更多
The expression of c-myc, c-fos of leukemic promyelocytes (HL-60 and acute promyelocytic leukemia cells) from 18 acute promyelocytic leukemia (APL) patients treated with all-trans retinoic acid (RA) in vitro was studie...The expression of c-myc, c-fos of leukemic promyelocytes (HL-60 and acute promyelocytic leukemia cells) from 18 acute promyelocytic leukemia (APL) patients treated with all-trans retinoic acid (RA) in vitro was studied. There was no expression of c-fos in HL-60 cells and APL cells from 17 patients. But in one case, a slight expression of c-fos in leukemic cells was observed, and the alteration of expression level was found during the treatment of the cells with RA in vitro. The expression of c-myc in HL-60 cells induced by RA was altered, decrease in the early, increase in the middle, and decline in the later stage were found. The c-myc expression in leukemic cells of eighteen APL patients was variable. There was c-myc expression in eleven APL cells, but no expression in the others. The APL cells with c-myc expression were treated with RA in vitro to observe the kinetic changes of c-myc RNA level. The results showed that the expression of c-myc was gradually decreased except in few cases. Using in situ hybridization technique for detecting the alteration of c-myc expression in leukemic cells of two APL patients. the high level of c-myc before RA treatment and low level of c-myc expression after obtaining complete remission induced by RA were found. The possibility of different proto-oncogenes implicated differentiation was discussed.展开更多
AIM: Eph receptors and ephrin ligands play a pivotal role in development and tissue maintenance. Since previous data have indicated an involvement of ephrin-B2 in epithelial healing, we investigated the gene expressi...AIM: Eph receptors and ephrin ligands play a pivotal role in development and tissue maintenance. Since previous data have indicated an involvement of ephrin-B2 in epithelial healing, we investigated the gene expression and downstream signaling pathways induced by ephrin-B mediated cell-cell signaling in intestinal epithelial cells. METHODS: Upon stimulation of ephrin-B pathways in IEC-6 cells with recombinant rat EphB1-Fc, gene expression was analyzed by Affymetrix rat genome 230 high density arrays at different time points. Differentially expressed genes were confirmed by real-time RT-PCR. In addition, MAP kinase pathways and focal adhesion kinase (FAK) activation downstream of ephrin-B were investigated by immunoblotting and fluorescence microscopy. RESULTS: Stimulation of the ephrin-B reverse signaling pathway in IEC-6 cells induces predominant expression of genes known to be involved into wound healing/cell migration, antiapoptotic pathways, host defense and inflammation. Cox-2, c-Fos, Egr-1, Egr-2, and MCP-1 were found among the most significantly regulated genes. Furthermore, we show that the expression of repair- related genes is also accompanied by activation of the ERKI/2 MAP kinase pathway and FAK, two key regulators of epithelial restitution. CONCLUSION: Stimulation of the ephrin-B reverse signaling pathway induces a phenotype characterized by upregulation of repair-related genes, which may partially be mediated by ERK1/2 pathways.展开更多
基金a grant from Hy-giene Fund of ZhejiangProvince, No. 2000A015
文摘BACKGROUND : c-fos and c-jun, the important immediate early genes (IEG), are regarded as the markers for the location and function of neuronal activity, as well as the third signal messengers, they couple the stress stimulation and the gene expression in neuron, and hippocampus is involved in the process of signal transmission after stress stimulation induced depression. OBJECTIVE: To observe the therapeutic effects of Bushen Yiqi (tonifying kidney to benefit qi), Huoxue Huayu (promoting blood circulation to dissipate blood stasis) and Ditan Kaiqiao (eliminating phlegm for resuscitation) on the expressions of c-Fos and c-Jun proteins in hippocampus and spontaneous behaviors of rats with post-stroke depression (PSD), and compare the results with those of fluoxetine, which is known to have definite effect on depression. DESIGN: A randomized controlled tna SETTING : Zhejiang College of Traditional Chinese Medicine MATERIALS : The trial was completed in Zhejiang College of Traditional Chinese Medicine from January to July in 2003. Fifty-six healthy adult Wistar male rats of clean grade, weighing (250±50) g, were randomly divided into 7 groups with 8 rats in each group: control group, model group, forced swimming group, Bushen Yiqi group; Huoxue Huayu, Ditan Kaiqiao group and fluoxetine group. The Bushen Yiqi Tang contained Renshen, Huangqi, Heshouwu, Gouqi, Shudi, etc., crude drugs 1 800 g/L. The Huoxue Huayu Tang contained Danshen, Chuanxiong, Chishao, Yujin, etc., crude drugs 3 600 g/L. The Ditan Kaiqiao Tang contained Banxia, Danxing, Changpu, Yuanzhi, etc., crude drug 1 000 g/b METHODS: ① Except the control group and forced swimming group, rats in the other groups were made into PSD models by deligating the bilateral common carotid artedes permanently. ② Rats in the control group, model group and forced swimming group were intragastncally perfused by saline (3 mL for each time); those in the Bushen Yiqi group, Huoxue Huayu, Ditan Kaiqiao group and fluoxetine group were intragastncally perfused with Bushen Yiqi Tang (18 g/kg), Huoxue Huayu Tang (9 g/kg), Ditan Kaiqiao Tang (9 g/kg) and fluoxetine (2.5 mg/kg) respectively, once a day. ③ At 55 days after model establishment, rats in the forced swimming group were managed according to the Porsolt's method. They were placed in water for 15 minutes, and then taken out and dned, no moving-time within 5 minutes was recorded at drying and 24 hours after drying. ④ Measurement of spontaneous behaviors: Except the forced swimming group, the spontaneous behaviors and activities (including horizontal and vertical movements) of rats were observed with the Open-Field method at 28, 42 and 56 days after administration in the other groups. ⑤ The expressions of c-Fos and coJun proteins in hippocampus were determined with the immunohistochemical method, the relative sectional area ratio and average objective gray value of c-Fos and c-Jun positive cells in hip- pocampus were measured with the computerized image analytical system. MAIN OUTCOME MEASURES: The spontaneous behaviors of rats, the relative sectional area ratio and average objective gray value of c-Fos and c-Jun positive cells in hippocampus were observed. RESULTS: Of the 56 rats, 1 died in the forced swimming group, and finally 55 rats were involved in the analysis of results. ① Results of spontaneous activities: At 28 days, the times of crossing movements were obviously fewer in the model group and fluoxetine group [(69.00±37.01), (98.11 ±36.68) times/3 minutes] than in the control group [(128.44±16.85) times/3 minutes, P 〈 0.01, 0.05], but those in the Bushen Yiqi group, Huoxue Quyu group and Ditan Kaiqiao group had no obvious differences as compared with those in the control group (P 〉 0.05). At 42 and 56 days, the times of crossing movements were obviously more in the Bushen Yiqi group, Huoxue Quyu group and Ditan Kaiqiao group [(106.44±31.24), (117.20±23.95), (134.80±28.18), (136.36±40.95) times/3 minutes; (117.33±35.91), (129.60 ±23.78), (131.90 ±26.81), (136.09±28.34) times/3 minutes] than in the model group [(64.00±17.51), (72.86±20.68) times/3 minutes, P 〈 0.01]. The times of rearing movements had no obvious differences among the groups for the three times (P 〉 0.05). ② The no moving-time within 5 minutes 24 hours after drying was obviously longer than that at drying in the forced swimming group. ③ The average objective gray values of c-Fos positive cells were not obviously different in the Bushen Yiqi group and Ditan Kaiqiao group from the control group (P 〉 0.05), but lower in the model group than in the control group (69.84±9.82, 75.78±5.89, P 〈 0.01), and higher in the forced swimming group than in the control group (85.97±10.99, P 〈 0.01); all higher in the fluoxetine group, Bushen Yiqi group, Huoxue Quyu group and Ditan Kaiqiao group than in the model group (81.27±10.73, 74.04±8.34, 83.29±9.89, 70.14±4.92, P 〈 0.05-0.01). The average objective gray values of c-Jun positive cells were obviously lower in the Bushen Yiqi group than in the control group (68.11 ±6.89, 79.58±5.86, P 〈 0.01), but all higher in the other groups than in the control group (84.68±7.15, 81.34 ±8.36, 97.51±10.55, 85.68±9.25, 86.19±10.98, P 〈 0.05-0.01); Those were obviously higher in the fluoxetine group, Huoxue Quyu group and Ditan Kaiqiao group than in the model group (P 〈 0.05-0.01 ), lower in the Bushen Yiqi group than in the model group (P 〈 0.05), all obviously lower in the Bushen Yiqi group, Huoxue Quyu group and Ditan Kaiqiao group than in the fluoxetine group (P 〈 0.01). The relative sectional area ratios of c-Fos and c-Jun positive cells had no obvious differences among the groups (P 〉 0.05). CONCLUSION : The methods of Bushen Yiqi, Huoxue Quyu and Ditan Kaiqiao can effectively treat PSD in rats, and the results were equivalent with those of fluoxetine, the actions of the above-mentioned drugs may correlated with their regulation to c-Fos and c-Jun expressions in hippocampus. PSD animal models can be successfully established by both permanent deligation of bilateral common carotid arteries and forced swimming, and the models induced by the former has similar basic cerebrovascular lesions as human stroke in clinic.
基金supported by Science and Technology Research and Development Plan of Shaanxi Province(Grant No.2011JE006)
文摘Objective:To investigate the expression and significance of the MMP-7,c-Jun and c-Fos in rat photoaging skin.Methods:A total of 45 SD rats were randomly divided into control group,model group,natural recovery group,physiological saline injection group and dermal pluripotent stem cells transplantation(DMSCs group),model group,natural recovery group,physiological saline injection group.DMSCs were treated with UV lamp irradiation to establish light aging skin model.Rats were then sacrificed after model prepared,no treatment was processed in the natural recovery group.Saline injections was adopted in saline group,DESCs group was treated with DESCs transplantation.Rats were sacrificed after 4 weeks.The expression of MMP-7,c-Jun and c-Kos were detected using the immunohistocheniical metluxl.Results:In model group,MMP 7positive expression was higher than that in the other 4 groups,but without statistically difference(P>0.05);c-Jun,c-Fos expression were higher than that in the control group and DESCs group(P<0.05),there was no significant difference comparing natural recovery group with physiological saline injection group(P>0.05).Conclusions:MMP-7,c-Jun and c-Fos can be used as diagnosis indicators in the early stage of light aging,and they jointly participate in its development.DMSCs transplants is effective in treating light aging skin.
基金the Natural Science Foundation of Sichuan Educational Bureau, No. Chuanjiaoji (2001) 149-01LA40
文摘BACKGROUND: Both c-Fos protein and nitricoxide synthase (NOS) have been used as general indexes in relative research about neurons, but it is lack of reports that c-Fos protein and NOS are applied synchronously to study the neurons of hypoxic fetal rats in uterus. OBJECTIVE: To study the effect of hypoxia in uterus on the expression of c-Fos protein and NOS in neurons of cerebral cortex from fetal rats and whether Angelica sinensis has the protective effect on these neurons in hypoxia. DESIGN: Randomized control experiment.SETTING : Department of Histology and Embryology, Luzhou Medical College.MATERIALS : Twelve adult female Wistar rats in oestrum and 1 male Wistar rat with bodymass from 220 to 250 g were chosen. Parenteral solution of Angelica sinensis mainly contained angelica sinensis, 10 mL/ampoule, was provided by Department of Agent of the Second Hospital Affiliated to Hubei Medical University (batch number: 01062310). METHODS : This experiment was completed in the Department of Histology and Embryology of Luzhou Medical College from September 2003 to June 2004. ①Twelve adult female Wistar rats in oestrum and 1 male Wistar rat were housed in one rearing cage. Vaginal embolus was performed on conceive female rat at 8: 00 am next day. On the 15^th conceiving day, all conceiving rats were divided randomly into three groups: control group, hypoxia group and Angelica group with 4 in each group. Rats in hypoxia group and Angelica group were modeled with hypotonic hypoxia in uterus. Angelica group: Rats were injected with 8 mL/kg Angelica sinensis injection through caudal veins before hypoxia. Hypoxia group: Rats were injected with the same volume of saline. Control group: Rats were not modeled and fed with normal way. ② Twenty embryos of rats were chosen randomly from each group and then routinely embedded in paraffin. Paraffin sections were cut from the brain of embryos to anterior fontanelle. Double-label staining was used to detect the expression of nNOS and c-Fos in neurons of cerebral cortex from embryos of rats. OLYMPUS Bx-50 microscope was used to observe sections and DP12 digit camera was also used under 400 times to detect types of cells. Under microscope, the number of c-Fos, NOS, c-Fos/NOS positive neurons in cerebral cortex from embryos of rats were counted in 2 fields with magnification of 400 in one section per animal. ③ The data in experiments were analyzed by one-way analysis of variance (ANOVA) followed by q test. MAIN OUTCOME MEASURES: ① Results of immunohistochemical double-label staining of c-Fos/NOS from cerebral cortex; ② Comparison of amount immunohistochemical double-label staining of c-Fos/NOS positive cells from cerebral cortex. RESULTS:① The positive NOS cells and c-Fos/NOS cells in the three groups were mainly distributed in cerebral cortex, but positive c-Fos neurons were not observed. ② Positive NOS cells and c-Fos/NOS cells in hypoxia group were more than those in control group (76.55±12.02, 50.45±10.39; 33.35±7.42, 26.35±6.67, P 〈 0.05), but those in Angelica group were less than those in hypoxia group (51.70±9.82, 35.65±8.37, P 〈 0.05). CONCLUSION: Hypoxia can stimulate the increase of expression of c-Fos protein and NOS in neurons of cerebral cortex. However, Angelica sinensis can decrease this expression so as to play a protective role in cerebral neurons of hypoxic fetal rats.
文摘The expression of c-myc, c-fos of leukemic promyelocytes (HL-60 and acute promyelocytic leukemia cells) from 18 acute promyelocytic leukemia (APL) patients treated with all-trans retinoic acid (RA) in vitro was studied. There was no expression of c-fos in HL-60 cells and APL cells from 17 patients. But in one case, a slight expression of c-fos in leukemic cells was observed, and the alteration of expression level was found during the treatment of the cells with RA in vitro. The expression of c-myc in HL-60 cells induced by RA was altered, decrease in the early, increase in the middle, and decline in the later stage were found. The c-myc expression in leukemic cells of eighteen APL patients was variable. There was c-myc expression in eleven APL cells, but no expression in the others. The APL cells with c-myc expression were treated with RA in vitro to observe the kinetic changes of c-myc RNA level. The results showed that the expression of c-myc was gradually decreased except in few cases. Using in situ hybridization technique for detecting the alteration of c-myc expression in leukemic cells of two APL patients. the high level of c-myc before RA treatment and low level of c-myc expression after obtaining complete remission induced by RA were found. The possibility of different proto-oncogenes implicated differentiation was discussed.
基金Supported by the German Research Society (DFG - SFB 585/A8) and the Dr. Heinz Maurer Grant KFB 1.7
文摘AIM: Eph receptors and ephrin ligands play a pivotal role in development and tissue maintenance. Since previous data have indicated an involvement of ephrin-B2 in epithelial healing, we investigated the gene expression and downstream signaling pathways induced by ephrin-B mediated cell-cell signaling in intestinal epithelial cells. METHODS: Upon stimulation of ephrin-B pathways in IEC-6 cells with recombinant rat EphB1-Fc, gene expression was analyzed by Affymetrix rat genome 230 high density arrays at different time points. Differentially expressed genes were confirmed by real-time RT-PCR. In addition, MAP kinase pathways and focal adhesion kinase (FAK) activation downstream of ephrin-B were investigated by immunoblotting and fluorescence microscopy. RESULTS: Stimulation of the ephrin-B reverse signaling pathway in IEC-6 cells induces predominant expression of genes known to be involved into wound healing/cell migration, antiapoptotic pathways, host defense and inflammation. Cox-2, c-Fos, Egr-1, Egr-2, and MCP-1 were found among the most significantly regulated genes. Furthermore, we show that the expression of repair- related genes is also accompanied by activation of the ERKI/2 MAP kinase pathway and FAK, two key regulators of epithelial restitution. CONCLUSION: Stimulation of the ephrin-B reverse signaling pathway induces a phenotype characterized by upregulation of repair-related genes, which may partially be mediated by ERK1/2 pathways.