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Background Lead is widely distributed. Lead exposure interferes with early life development in zebrafish, but the mechanisms by which lead exposure affects skeletal development and cardiac development are not clear as yet. Objective To investigate the molecular mechanisms of bone development and cardiac development toxicity induced by lead acetate exposure. Methods Zebrafish embryos were exposed to different concentrations of lead acetate (0, 6, 12, 24, and 48 μmol·L−1) for 3 h post-fertilization (3 hpf) until 5 d post-fertilization (5 dpf). The malformation phenotypes of 5 dpf were counted, and the mRNA expressions of spinal development-related genes (bmp2b, bmp4, bmp9, runx2a, runx2b) and heart development-related genes (nkx2.5, myh6, myh7) were detected by quantitative PCR (qPCR). Expressions of genes of development-related regulatory pathways including Wnt/β-catenin pathway (wnt5a, wnt8a, wnt10a, β-catenin) and TGF-β pathway (tgf-β1, tgf-β2) as well as key molecule eph of Eph-Ephrin signaling were analyzed. Results At 5 dpf, the zebrafish in the lead acetate treated groups showed deformed phenotypes including spinal curvature and pericardial sac edema compared to the control group. In the lead acetate groups at 24 and 48 μmol·L−1, the spinal curvature deformity rates reached 26.47% and 71.52% (P<0.01) respectively. The qPCR results revealed that the expression levels of spinal development-related genes bmp2b, bmp4, bmp9, runx2a, and runx2b were downregulated in the 48 μmol·L−1 exposure group compared to the control group by 82.8%, 58.0%, 88.7%, 85.5%, and 69.2%, respectively (P<0.05 or P<0.01); the expression levels of heart development-related genes myh6, myh7, and nkx2.5 were down-regulated by 63.7%, 58.9%, and 55.2%, respectively (P<0.01); the expression levels of wnt8a and β-catenin in the Wnt/β-catenin pathway were down-regulated by 71.5% and 47.3% (P < 0.05 or P < 0.01), respectively; the expression level of tgf- β1 in the TGF-β pathway was down-regulated by 67.5% (P<0.01); the expression level of eph was down-regulated by 86.9% (P<0.01). Conclusion Lead acetate exerts developmental toxic effects on zebrafish heart and bone by down-regulating the expressions of genes related to spinal development and heart development, as well as inhibiting development-related Wnt/β-catenin and TGF-β pathways and Eph-Ephrin signaling, causing malformed phenotypes such as spinal curvature and pericardial sac edema.
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Objective:To investigate the effects of hippocampal injection of tyrosine kinase receptor binding protein B3(Ephrin-B3) agonist on spontaneous seizures and the expression of hippocampal secretory glycoprotein (Reelin) and phosphorylated adaptor protein (p-Dab1) in epileptic model rats.Methods:Seventy-eight rats were randomly divided into control group and model group according to body mass matching with 39 rats in each group.The rats in control group were fed normaly, and the rats in model group were established epilepsy model by intraperitoneal injection of lithium chloride pilocarpine. The hippocampal tissues were taken in the acute phase (7 days), quiescent phase (14 days) and chronic phase (60 days) after the successful induction of status epilepticus. The levels of Reelin protein and p-Dab1 protein in the hippocampal tissues of epileptic model rats and normal rats were detected by immunohistochemistry and Western blot.And thirteen rats were randomly selected at each time point. Another 48 rats were randomly divided into normal Fc-control group, normal EphB3-Fc group, epilepsy Fc-control group and epilepsy EphB3-Fc group, with 12 rats in each group. Rats in the first two groups were fed normally, and those in the latter two groups were established epileptic model. Seven days after modeling, all rats were injected into bilateral hippocampus with EphB3-Fc (Ephrin-B3 agonist) and FC control (control agent of Ephrin-B3 agonist) according to the grouping, once a day for 7 days. After administration, the changes of behavior and EEG were observed within two weeks. At the same time, the expression of Reelin protein and p-Dab1 protein were detected by immunohistochemistry and Western blot. SPSS 21.0 was used for statistical analysis, One-way ANOVA was used for multi group comparison, and Tukey's test was used for pairwise comparison.Results:The results of immunohistochemistry and Western blot showed that compared with the control group, the levels of Reelin and p-Dab1 protein in hippocampus of model group decreased significantly at 7, 14 and 60 days after epilepsy (all P<0.01). The results of immunohistochemistry showed that compared with epilepsy Fc-control group, the levels of p-Dab1 ((0.41±0.04), (0.58±0.06), P<0.05) in epilepsy EphB3-Fc group increased significantly.Western blot result showed that the level of p-Dab1 in epilepsy EphB3-Fc group increased compared with that of epilepsy Fc-control group (1.34±0.04), (2.26±0.10), P<0.01). Compared with epilepsy Fc-control group, epilepsy EphB3-Fc group showed less average seizure duration ((39.00±1.79)s, (26.50±1.87)s; t=23.21, P<0.01), less frequencies ((2.00±0.89), (0.50±0.55); t=2.32, P<0.01) and less latent period ((6.33±1.37)day, (12.50±1.87)day; t=2.52, P<0.01) in spontaneous recurrent seizures. Compared with epilepsy Fc-control group, epilepsy EphB3-Fc group showed lower average amplitude ((37.30±1.21)μV, (29.00±1.41)μV; t=25.14, P<0.01), less average seizure duration ((5.35±0.19)s, (2.35±0.19)s; t=3.13, P<0.01). Conclusion:Ephrin-B3 alleviated spontaneous recurrent seizures by upregulating Reelin and p-Dab1 in temporal lobe epilepsy rat.
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Background: Colorectal cancer (CRC) is rated as the second cause of cancer death. Genetic determinants are considered as driving forces in the development of sporadic CRC. Single-nucleotide polymorphisms (SNPs), due to their abundance in the human genome with collectively huge effect on cellular signaling pathways, are attributed as the main genetic factor in disease susceptibility including cancers. MicroRNAs are contributing to posttranslational gene regulation. They exert their regulatory function by binding to their specific recognition sequences located at 3'-untranslated region (UTR) of mRNAs. In the present study, we have elucidated the role of rs12904, a naturally occurring SNP, in the recognition site of miR200c in the 3'UTR of ephrin A1 ligand gene, in the development of sporadic CRC in the Iranian population. Materials and Methods: A case–control study using 152 CRC patients and 160 noncancerous counterparts was conducted to determine the rs12904 genotypes using polymerase chain reaction–restriction fragment length polymorphism method. Results: The results revealed no significant association between the rs12904 and sporadic CRC (odds ratio = 0.97, 95% confidence interval = 0.70–1.34). The frequency of genotypes and also alleles of the mentioned polymorphism were not significantly different between case and control groups (P = 0.765 and P = 0.847, respectively). Conclusion: The results suggest that this polymorphism probably has not a crucial role in the Iranian CRC risk and is not an important potential risk factor in molecular diagnostics of mentioned disease among the Iranian population.
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Objective@#To investigate the difference and correlations of the EphrinA1, vascular endothelial growth factor (VEGF) expression and microRNA (miRNA)-210 in the kidney tissue of rats in the unilateral ureteral obstruction (UUO) model. And to understand the regulation mechanism of the three factors in the occurrence of renal tissue injury in rats.@*Methods@#Using unilateral ureteral ligation to establish a model of hydronephrosis in mice (except for the NC group), and they wrere randomly divided into an acute hydronephrosis group (UUO group) and a false surgical control group (NC group). The UUO group was divided into four groups (UUO 2 d group, UUO 5 d group, UUO 9 d group, and UUO 14 d group), and eight mice in each group. The pathological changes of renal tissue were observed by hematoxylin-eosin (HE) staining. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression of EphrinA1, VEGF and miRNA-210; Western blot was used to detect the protein expression of EphrinA1 and VEGF.@*Resulsts@#Hydronephrosis was not shown in the NC group, and hydronephrosis and inflammatory cell infiltration were observed in the UUO group. Compared with NC group, the mRNA expression of EphrinA1 , VEGF and miRNA-210 were up-regulated in UUO 2 d group (P<0.05). With the extension of the time of hydronephrosis, the expressions of all three factors were down-regulated in 9 d and 14 d groups compared with 2 d and 5 d groups, and reached the lowest point at 14 d (P<0.05); Western blot result indicated that the expression of EphrinA1 and VEGF in renal tissue of UUO 2 d and 5 d group was increased compared with NC group (P<0.05).@*Conclusions@#The UUO mouse model verified that miRNR-210 participated in hydronephrosis. The consistency of EphrinA1, VEGF, and miRNA-210 indicated that the three factors played an important role in the occurrence and development of UUO.
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Objective To investigate the difference and correlations of the EphrinA1,vascular endothelial growth factor (VEGF) expression and microRNA (miRNA)-210 in the kidney tissue of rats in the unilateral ureteral obstruction (UUO) model.And to understand the regulation mechanism of the three factors in the occurrence of renal tissue injury in rats.Methods Using unilateral ureteral ligation to establish a model of hydronephrosis in mice (except for the NC group),and they wrere randomly divided into an acute hydronephrosis group (UUO group) and a false surgical control group (NC group).The UUO group was divided into four groups (UUO 2 d group,UUO 5 d group,UUO 9 d group,and UUO 14 d group),and eight mice in each group.The pathological changes of renal tissue were observed by hematoxylin-eosin (HE) staining.Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression of EphrinA1,VEGF and miRNA-210;Western blot was used to detect the protein expression of EphrinA1 and VEGF.Resulsts Hydronephrosis was not shown in the NC group,and hydronephrosis and inflammatory cell infiltration were observed in the UUO group.Compared with NC group,the mRNA expression of EphrinA1,VEGF and miRNA-210 were up-regulated in UUO 2 d group (P ＜0.05).With the extension of the time of hydronephrosis,the expressions of all three factors were down-regulated in 9 d and 14 d groups compared with 2 d and 5 d groups,and reached the lowest point at 14 d (P ＜0.05);Western blot result indicated that the expression of EphrinA1 and VEGF in renal tissue of UUO 2 d and 5 d group was increased compared with NC group (P ＜ 0.05).Conclusions The UUO mouse model verified that miRNR-210 participated in hydronephrosis.The consistency of EphrinA1,VEGF,and miRNA-210 indicated that the three factors played an important role in the occurrence and development of UUO.
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The Eph receptors and their ligand Ephrins are closely associated with angiogenesis,cell migration,neuronal local-ization and embryonic development.More and more studies have shown that the Eph receptor and Ephrins are involved in the occur-rence and development of various cancers.In this article,we will focus on the Eph receptor family involved in the formation and devel-opment of lung cancer and metastasis,drug resistance and other mechanisms as well as their potential as targeted therapy of lung canc-er.
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ObjectiveTo investigate the effects of long-term oxygen exposure on the pulmonary microvascular development and the expression of Ephrin-B2 of lungt issue in neonatal mice.MethodsForty-eight 2-day-old Kunming mice were randomly divided into hyperoxia group and air group, with 24 mice in each group. Mice in hyperoxia group were exposed to 70% oxygen to establish a model of bronchopulmonary dysplasia (BPD). Six mice from each group were sacrificed at 3, 7, 14 and 21 days of age, and lung tissue was collected for further test. The lung sections were stained with hematoxylin and eosin for histological evaluation, radial alveolar counts (RAC) and microvessel density (MVD) measurement by CD34 immunohistochemistry. Location and expression of Ephrin-B2 in lung tissue were measured by immunohistochemistry. Ephrin-B2 mRNA and protein levels were detected by fluorescent quantitative reverse transcriptase-polymerase chain reaction and Western blot, respectively. Two independent samplest-test was used for statistical analysis. Results(1) Pathological changes: The pathology of lung tissue in hyperoxia group showed typical BPD-like changes with advancing postnatal age, presenting mainly with simplified alveolar development and decreased microvessel number. Compared with the air group, RAC and MVD were significantly decreased in 14-day-old mice (6.067±0.432 vs 6.950±0.243,t=4.365,P<0.05; 4.133±0.476 vs 4.867±0.472,t=2.680,P<0.01) and 21-day-old mice in the hyperoxia group (8.050±0.362 vs 9.817±0.487,t=7.127,P<0.05; 4.333±0.532 vs 6.017±0.937,t=3.828,P<0.01). (2) Location and expression of Ephrin-B2: Ephrin-B2 was mainly expressed in alveolar epithelial cells, and weakly expressed in alveolar septum. Compared with the air group, the average optical density of Ephrin-B2 was significantly decreased in 7-day-old (0.146±0.013 vs 0.153±0.009), 14-day-old (0.140±0.007 vs 0.161±0.006) and 21-day-old mice in the hyperoxia group (0.138±0.008 vs 0.166±0.009)(t=-2.049,-9.442 and-10.087, allP<0.05). (3) Ephrin-B2 mRNA and protein levels: The Ephrin-B2 mRNA levels in 14-day-old (0.65±0.14 vs 1.05±0.16,t=4.609,P<0.01) and 21-day-old mice (0.57±0.09 vs 1.13±0.18,t=6.816,P<0.01) were significantly lower in hyperoxia group than in the air group. The Ephrin-B2 protein levels were also significantly lower in hyperoxia group than in the air group in 21-day-old mice (0.13±0.03 vs 0.29±0.08,t=4.587,P=0.000).ConclusionsOxygen-induced BPD model mice have simplified alveolar development, reduced MVD and decreased expression of Ephrin-B2 in lung tissue, which may play an important role in the pathogenesis of BPD.
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Objective Recent researches indicate that Eph/ephrin signaling pathway is possibly related to adult neurogenesis after cerebral injury..With brief introduction of their structures and interactions,the review focus on their possible mechanism in adult neurogenesis.Methods The literatures between 2010 and 2015 were retrieved following online databases:PUBMED,ScienceDirect,Wanfang and CNKI database.The key words used in the reasearch were Eph,ephrin,cerebral injury,adult neurogenesisand so on.Results Totally 42 related articles were enrolled.And these papers discribed how researchers performed their experiments and further explained Eph/ephrin 's vital roles in adult neurogenesis.Conclusion Eph/ephrin signaling can influence adult neurogenesis after cerebral injury.positively or negatively.And Akt may be a downstream signaling molecule of Eph/ephrin that change the progress of adult neurogenesis.However,the detailed mechanisms remain to be further study.
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Eph receptors and their ligands, ephrins, are abundantly expressed in neuroepithelial cells of the early embryonic brain. Overstimulation of Eph signaling in vivo increases apoptotic cell death of neuroepithelial cells, whereas null mutation of the Eph gene leads to the development of a larger brain during embryogenesis. Thus, it appears that Eph-ephrin signaling plays a role in regulating apoptotic cell death of neuroepithelial cells, thereby influencing brain size during embryonic development. Interestingly, Eph-ephrin signaling is bi-directional, with forward signaling from ephrin- to Eph-expressing cells and reverse signaling from Eph- to ephrin-expressing cells. However, it is not clear whether this forward or reverse signaling plays a role in regulating the size of the neuroepithelial cell population during early brain development. Also, Eph receptors and their corresponding ligands are mutually exclusive in their expression domains, and they encounter each other only at interfaces between their expression domains. This expression pattern may be a critical mechanism for preventing overstimulation of Eph-ephrin signaling. Nevertheless, Eph receptors are co-expressed with their corresponding ligands in certain brain regions. Recently, two studies demonstrated that brain region-specific apoptosis may be triggered by the overlapping expression of Eph and ephrin, a theme that will be explored in this mini-review.
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Female , Pregnancy , Apoptosis , Brain , Cell Death , Embryonic Development , Ephrins , Ligands , Neuroepithelial Cells , Receptor, EphA1 , Receptors, Eph FamilyABSTRACT
Background : Ephrin A4 is one of the ephrin ligand molecules belonging to the tyrosine kinases receptor family. It was originally identified in a T-lymphoma cell line and seen to be expressed in human adult tissue as well as several tumor types. In our previous study, we showed the unique pattern of ephrin A4 immunohistochemical staining, which differed according to the type of examined bone specimens (normal bone, primary, and metastatic osteosarcoma lesions). The aim of the present study is to evaluate the prognostic impact of ephrin A4 expression in a group of primary osteosarcoma patients. Materials and Methods : Ephrin A4 immunohistochemical expression was carried out on 47 primary osteosarcoma cases. Results : Ephrin A4 was expressed in 82.9% of osteosarcoma cases with cytoplasmic localization in 58.9% of positive cases. The cytoplasmic pattern was significantly associated with aggressive histopathological types of osteosarcoma (P = 0.02), advanced stage (P = 0.04), the presence of metastasis (P = 0.03), inferior response to neoadjuvent chemotherapy (P = 0.04), and tended to be associated with a shorter event-free survival (P = 0.09). Conclusions : The cytoplasmic pattern of ephrin A4 could identify a subgroup of primary osteosarcoma patients with a high liability for progression, poor prognosis, and inferior response to chemotherapy.
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Antineoplastic Agents/therapeutic use , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Bone Neoplasms/therapy , Ephrin-A4/biosynthesis , Humans , Immunohistochemistry , Neoplasm Staging , Osteosarcoma/metabolism , Osteosarcoma/pathology , Osteosarcoma/therapy , Prognosis , Proportional Hazards Models , Treatment Outcome , Biomarkers, Tumor/analysisABSTRACT
EphA/ephrin-A mediated signaling has emerged as a key mechanism regulating axon guidance and topographic mapping, particularly in the well-characterized visual system from the retina to the superior colliculus (SC). In this study, EphA8 bacterial artificial chromosome (BAC) was manipulated to contain a floxed eGFP and human ephrin-A5 expression cassette using homologous recombination method. In the mice containing the recombinant BAC, it was shown that GFP is expressed in an anterior>posterior gradient in the SC. Furthermore, when these mice were crossed with the transgenic mice expressing Cre under the EphA8 promoter, it was evident that a GFP expression cassette was eliminated, and that human ephrin-A5 was ectopically expressed in the anterior region of the SC. This transgenic model would be useful to analyze the role of ephrin-A5 in the SC during the retinocollicular topography formation.
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Animals , Humans , Mice , Axons , Chromosomes, Artificial, Bacterial , Ephrin-A5 , Homologous Recombination , Mice, Transgenic , Retina , Superior ColliculiABSTRACT
Background: Several molecules that may have a role in tumor proliferation, differentiation and invasion, have been detected in thyroid carcinoma. Some of these molecules are NIS, c-MET, TIMP1 an ephrinB2. Aim: To detect the presence of these molecules in tissue samples of thyroid carcinoma and relate their expression to the biological behavior of the tumor. Material and Methods: Tissue samples were prospectively obtained from 35 patients operated for a papillary thyroid carcinoma. Twelve patients had regional lymph node involvement. NIS, c-MET, TIMP1 and EphrinB2 were detected by real time polymerase chain reaction(RT-PCR) and immunohistochemistry. Results: The expression of markers by RT-PCR was non significantly higher among tumors with lymph node involvement. Immunohistochemistryshowed a significantly lower nuclear expression and a higher cytoplasmatic expression of EphrinB2 in tumors with lymph node involvement. Conclusions: Immunohistochemical expression of EphrinB2 could be useful for the initial staging of papillary thyroid carcinoma.
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Humans , Adenocarcinoma, Papillary/genetics , Adenocarcinoma, Papillary/metabolism , Thyroid Neoplasms/genetics , Thyroid Neoplasms/metabolism , /genetics , /metabolism , Gene Expression Regulation, Neoplastic , Immunohistochemistry , Tissue Inhibitor of Metalloproteinase-1/genetics , Tissue Inhibitor of Metalloproteinase-1/metabolism , Lymphatic Metastasis , Biomarkers, Tumor , Neoplasm Invasiveness , Proto-Oncogene Proteins c-met/genetics , Proto-Oncogene Proteins c-met/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Symporters/metabolismABSTRACT
Objective To investigate the role of PI_3 K/Akt signal pathway in Ephrin-Al gene mediated invasion,metastasis of Huh-7 cells.Methods Western blot was used to test the protein expression of phosphatidylinositol 3-kinase(PI_3 K)and mitogen-activated protein kinase(MAPK)after Huh-7 cells were treated with Ephrin-A1/Fc fusion protein.According to the protein expression,LY294002 was used to block PI_3 K/Akt pathway specifically,then p-Akt protein expression,mobility and invasive ability of Huh-7 cells were examined.Results In Huh-7 cells actived by Ephrin-Al/Fc fusion protein,p-Akt expression was higher than that in control group(t=4.564,P＜0.05),but there was no difference of p-p38MAPK expression between Ephrin-Al/Fc fusion protein group and IgG/Fc fusion protein group(P＞0.05).PI_3 K/Akt pathway was specifically blocked by LY294002,the p-Akt protein expression decreased in Huh-7 cells,and the mobility and invasive ability mediated by Ephrin-Al in Huh-7 cells decreased(P＜0.05).Conclusions PI_3 K/Akt pathway effects an important role in mobility and invasive ability of Huh-7 cells mediated by Ephrin-A1.
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Objective To study changes of expression in Ephrin and its receptors in DRG neurons after peripheral nerve injury. Methods A rat model of unilateral crushed sciatic nerve was prepared, and changes in the expression pattern of Ephrin B1, Eph B1、Eph B2、Eph B3、EphA4 and RYK in DRG neurons in the rats crushed unilateral sciatic nerve were estimated by the number of positive staining cells in DRG, and the percentage of positive cells as well as the cell size.Results After peripheral nerve injury, the expression of Ephrin B1 significantly decreased, but there was no change in expression of Eph B1、Eph B2、Eph B3 or Eph A4, RYK expression was intensely induced in DRG neurons. Conclusion Ephrin B1 and RYK showed very significant expression changes in ERG neurons after peripheral nerve injury, and may be a component factor process of peripheral never regeneration.
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Osteoclastic bone resorption and osteoblastic bone formation are coordinated as a coupled mechanism to effect the development of bone and to maintain bone homeostasis. Recently reported Eph/ephrin bidirectional signaling between osteoclasts and osteoblasts plays a pivol role in bone homeostasis and casts new light on coupling of bone resorption and bone formation, which is gaining more and more attention in researches of bone biology and bone diseases. The present article aims to address the researches on the Eph/ephrin bidirectional signaling between osteoblasts and osteoclasts with molecular constitution, mechanism of the signal transduction, biological significance and so on.
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Bidirectional signal transduction is a newly elucidated mechanism in intercellular communication. The bidirectional signal transduction mediated by the Eph-ephrin is an important representative in this field. The Eph family receptor tyrosine kinases and their membrane-bound ligands, the ephrins, play pivotal roles in the development of nervous system, angiogenesis, etc. The signal transduction into cells by Eph receptors is the forward signal, whereas the signal transduction by ephrins is the reverse signal. Based on their molecular structures, the ephrins can be divided into two subclasses, i.e. ephrinA and ephrinB. The ephrinBs are transmembrane proteins, which can activate FAK, JNK and Wnt signal transduction pathways through phosphotyrosine-dependent signaling and PDZ-binding motif-dependent signaling. The ephrinAs are glycosylphosphotidylinositol (GPI) anchored proteins, which can also mediate reverse signal transduction.
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This study was aimed to map the 1 kb cis-acting DNA of ephA8 gene, which regulates the spatial and temporal expression in the anterior mesencephalon. It was demonstrated that the 1 kb ephA8 enhancer DNA was sufficient to drive the lacZ expression to the anterior mesencephalon under the human beta-globin minimal promoter. It was also found that a 180 bp within the 1 kb enhancer DNA was highly conserved between human and mouse, and that this 180 bp DNA was capable of inducing the lacZ expression in the anterior mesencephalon under the ephA8 or human beta-globin basal promoter. Further analysis using 5'-55 bp deleted or 3'-55 bp deleted mutant DNA revealed that the 55 bp portion present at the 3'-end of 180 bp DNA was critical for the regulation of ephA8 gene expression in the anterior mesencephalon. Taken together, these results indicate that 180 bp ephA8 enhancer DNA contains cisacting elements for the regulation of ephA8 gene expression in the anterior mesencephalon.
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Animals , Humans , Mice , beta-Globins , DNA , Gene Expression , Mesencephalon , Mice, TransgenicABSTRACT
Objective To study the relationship between Ephrin-A1 and its receptor with angiogenesis in hepatocellular carcinoma(HCC).Methods Immunohistochemistry staining method(S P methods)and reverse transcription polymerase chain reaction(RT-PCR) were used to determine the protein and mRNA expression of Ephrin-A1 and its receptor EphA1、EphA2 in tumor tissues and their corresponding adjacent liver tissues from 52 HCC patients;then,analyse of the relationship between Ephrin-A1 and clinicopathologyfactor and microvessel density(MVD) in HCC was made.Results The protein expression rate of Ephrin-A1 and EphA1,EphA2 in HCC was 59.6%(31/52),53.8%(28/52)and 17.3%(9/52),respectively,but in the paired liver tissues adjacent to HCC the expression rate was 23.1%(12/52),and respectively.The protein expression rate of Ephrin-A1 and EphA1 was significantly higher than that in the paired liver tissues adjacent to HCC(P0.05).The mRNA express rate of Ephrin-A1 and EphA1 in HCC [67.3%(35/52) and 73.7%(38/52)] were prominently higher than those in the paired liver tissues adjacent to HCC [42.3%(22/52) and 48.1%(25/52)](P0.05).The higher expression of Ephrin-A1 was correlated with the AFP level and thrombus in the portal vein(P
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The Eph protein family,consisting of Eph receptors and their corresponding membrane-anchored protein ligands-Ephrin,is no doubt the largest receptor protein tyrosine kinases family till now.Interactions between Eph receptors and Ephrin ligands based on their special structure might make the Eph protein family one of new targets of disease′s treatment and consequently studies related to Eph proteins and their receptors have draw more and more attention.This overview will focus on recent progresses in the classification,gene expression,protein structure,function and protein-receptor interactions of the Eph protein family and their receptors.Much of the focus of this overview is on their physiological and pathophysiological role in nervous system and their therapeutic perspective from several aspects.