RESUMO
BACKGROUND AND OBJECTIVES: This study aimed to investigate the clinical characteristics of infantile Kawasaki disease (KD), and to evaluate early diagnostic features of KD in febrile infants. SUBJECTS AND METHODS: We retrospectively reviewed the medical records of 64 KD patients from January 2010 to October 2014. There was an analysis of the clinical, laboratory data of the infants versus children groups. Furthermore, the clinical and laboratory data of infantile KD patients were compared with 16 infants who were admitted for other acute febrile diseases. RESULTS: A total of 64 patients with KD were identified; 20 (31.3%) were infants; 44 (68.8%) were >1 year old children. Incomplete KD was much more common in infants (n=13, 65.0%) than in children group (n=14, 31.8%) (p=0.013). The infants were characterized by significantly higher rates of inflammatory changes at the Bacille Calmett-Guérin (BCG) inoculation site (p<0.001), but lower rates of changes in the extremities (p=0.029) and cervical lymphadenopathy (p=0.006). The serum levels of platelet after 1 week (p=0.005), C-reactive protein (p=0.038), and N-terminal pro-brain natriuretic peptide (NT-proBNP) (p=0.026) were all significantly higher in the infants group. Comparing the infants with KD versus the other acute febrile diseases, there were significantly higher serum levels of erythrocyte sedimentation rate (p=0.002), C-reactive protein (p=0.046) and NT-proBNP (p=0.001) for the infants with KD group. CONCLUSION: BCGitis and higher levels of NT-proBNP can be helpful for early diagnosis of the incomplete KD in infants, and may be a good predictor of KD in acute febrile infants, when combined with other acute phase reactants.
RESUMO
The binding of interleukin-6 (IL-6) cytokine family ligands to the gp130 receptor complex activates the Janus kinase (JAK)/ signal transducer and activator of transcription 3 (STAT3) signal transduction pathway, where STAT3 plays an important role in cell survival and tumorigenesis. Constitutive activation of STAT3 has been frequently observed in many cancer tissues, and thus, blocking of the gp130 signaling pathway, at the JAK level, might be a useful therapeutic approach for the suppression of STAT3 activity, as anticancer therapy. AG490 is a tyrphostin tyrosine kinase inhibitor that has been extensively used for inhibiting JAK2 in vitro and in vivo. In this study, we demonstrate a novel mechanism associated with AG490 that inhibits the JAK/STAT3 pathway. AG490 induced downregulation of gp130, a common receptor for the IL-6 cytokine family compounds, but not JAK2 or STAT3, within three hours of exposure. The downregulation of gp130 was not caused by enhanced degradation of gp130 or by inhibition of mRNA transcription. It most likely occurred by translation inhibition of gp130 in association with phosphorylation of the eukaryotic initiation factor-2alpha . The inhibition of protein synthesis of gp130 by AG490 led to immediate loss of mature gp130 in cell membranes, due to its short half-life, thereby resulting in reduction in the STAT3 response to IL-6. Taken together, these results suggest that AG490 blocks the STAT3 activation pathway via a novel pathway.
RESUMO
We previously reported that nidogen is an extracellular matrix protein regulating Schwann cell proliferation and migration. Since Schwann cells play a critical role in peripheral nerve regeneration, nidogen may play a role in it via regulation of Schwann cells. Here, we demonstrate direct evidence that nidogen induces elongation of regenerative axon growth of adult sensory neurons, and that the effect is Schwann cell dependent. Continuous infusion of recombinant ectodomain of tumor endothelial marker 7, which specifically blocks nidogen function in Schwann cells, suppressed regenerative neurite growth in a sciatic nerve axotomy model. Taken together, it is likely that nidogen is required for proper regeneration of peripheral nerves after injury.
Assuntos
Glicoproteínas de Membrana/fisiologia , Regeneração Nervosa , Neuritos/fisiologia , Células de Schwann/fisiologia , Células Receptoras Sensoriais/fisiologia , Animais , Axotomia , Movimento Celular , Proliferação de Células , Masculino , Proteínas de Membrana/farmacologia , Proteínas do Tecido Nervoso/farmacologia , Neuritos/efeitos dos fármacos , Neuritos/ultraestrutura , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/farmacologia , Células de Schwann/citologiaRESUMO
Nerve injury-induced activation of signal transducer and activator of transcription 3 (STAT3) in sensory neurons and Schwann cells has been implicated in peripheral nerve regeneration. In this study, we investigated the role of gp130-related cytokines including interleukin-6 (IL-6), ciliary neurotrophic factor (CNTF), and leukemia inhibitory factor (LIF) in STAT3 activation in dorsal root ganglion neurons, Schwann cells, and endoneurial fibroblasts. We found that IL-6, but not CNTF or LIF, activated STAT3 in Schwann cells. However, CNTF and LIF, but not IL-6, activated STAT3 in dorsal root ganglion neurons. Furthermore, LIF was the primary activator of STAT3 in endoneurial fibroblasts. These findings indicate that gp130 cytokines may have cell type-specific roles in peripheral nerve regeneration.
Assuntos
Receptor gp130 de Citocina/metabolismo , Citocinas/metabolismo , Fibroblastos/metabolismo , Gânglios Espinais/metabolismo , Neurônios/metabolismo , Fator de Transcrição STAT3/metabolismo , Células de Schwann/metabolismo , Animais , Western Blotting , Células Cultivadas , Fator Neurotrófico Ciliar/metabolismo , Imunofluorescência , Interleucina-6/metabolismo , Fator Inibidor de Leucemia/metabolismo , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/metabolismoRESUMO
Capsaicin has been shown to have anti-carcinogenic effects on various tumor cells through multiple mechanisms. It was recently reported that capsaicin inhibited interleukin-6 (IL-6)-induced activation of signal transducer and activator of transcription 3 (STAT3), an anti-apoptotic transcription factor. Here we demonstrate that capsaicin induced downregulation of the IL-6 receptor gp130 within 2h in glial tumors. The downregulation of gp130 was not caused by enhanced degradation of gp130 or by inhibition of mRNA transcription. The downregulation was attributed to translation inhibition of gp130, which was associated with activation of endoplasmic reticulum (ER) stress. The depletion of the intracellular pool of gp130 by capsaicin and an ER stress inducer led to an immediate loss of the IL-6 response due to the short half-life of membrane localized gp130. These results suggest a novel mechanism for the anti-tumor effect of capsaicin.
Assuntos
Antineoplásicos/farmacologia , Capsaicina/farmacologia , Receptor gp130 de Citocina/antagonistas & inibidores , Retículo Endoplasmático/efeitos dos fármacos , Interleucina-6/antagonistas & inibidores , Fator de Transcrição STAT3/antagonistas & inibidores , Animais , Linhagem Celular Tumoral , Receptor gp130 de Citocina/biossíntese , Regulação para Baixo , Retículo Endoplasmático/metabolismo , Interleucina-6/metabolismo , Biossíntese de Proteínas/efeitos dos fármacos , Ratos , Fator de Transcrição STAT3/metabolismo , Transdução de SinaisRESUMO
Signal transducer and activator of transcription 3 (STAT3) regulates gene transcription in response to cytokines and growth factors. In the central nervous system, STAT3 plays a role in neuroprotection and reactive gliosis after lesions. During peripheral nerve regeneration, a nerve injury-induced up-regulation of cytokines and growth factors accompanies STAT3 activation in sensory neurons and Schwann cells (SCs) even though its molecular details and functions are unknown. We then analyzed the ligands and functions of STAT3 activation in RT4 schwannoma cells and adult SCs in vitro and in vivo. We have identified that interleukin-6 (IL-6), but not ciliary neurotrophic factor, leukemia inhibitory factor, or ligands for receptor tyrosine kinases, activates STAT3 in SCs. The IL-6/STAT3 signaling in primary SCs and RT4 cells induced the gene expression of glial fibrillary acidic protein (GFAP), which is known to be required for the proper regeneration of the injured nerves. Finally, the GFAP induction in the sciatic nerves after injury was significantly delayed in IL-6-deficient mice. These findings indicate that IL-6 plays an important role in STAT3-dependent GFAP induction in SCs during peripheral nerve regeneration.
Assuntos
Proteína Glial Fibrilar Ácida/biossíntese , Interleucina-6/fisiologia , Células de Schwann/metabolismo , Degeneração Walleriana/metabolismo , Animais , Western Blotting , Linhagem Celular , Fator Neurotrófico Ciliar/farmacologia , Receptor gp130 de Citocina/fisiologia , Citocinas/biossíntese , Citocinas/genética , Imunofluorescência , Genes Reporter/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/genética , Interleucina-6/genética , Fator Inibidor de Leucemia/farmacologia , Luciferases/biossíntese , Luciferases/genética , Camundongos , Camundongos Knockout , Fosforilação , RNA Interferente Pequeno/farmacologia , Ratos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição STAT3/biossíntese , Fator de Transcrição STAT3/genética , Nervo Isquiático/citologia , Nervo Isquiático/metabolismoRESUMO
Methylglyoxal (MGO) is an endogenous dicarbonyl compound that is highly produced in hyperglycemic conditions. It forms advanced glycation endproducts that are believed to contribute, as etiological factors, to the pathophysiology of diabetic complications. In addition, MGO suppresses cell viability through the induction of apoptosis in vitro. In this study, we have, for the first time, demonstrated the effect of MGO on the gp130 cytokine-induced signal transducer and activator of transcription 3 (STAT3) responses in RT4 schwannoma, PC12 pheochromocytoma and U87MG glioma cells. At dose that very mildly affects cell viability, MGO rapidly induces endocytotic degradation of gp130, which involves the di-leucine internalization motif in the cytoplasmic domain of gp130, without affecting other growth factor receptors. Concomitant inhibition of basal and interleukin-6-induced STAT3 activation was observed following pre-treatment with MGO. The inhibitory effect of MGO on the gp130/STAT3 signaling was prevented by the pre-treatment with an advanced glycation endproduct scavenger aminoguanidine. Finally, these deleterious effects of MGO on STAT3 signaling led to down-regulation of a STAT3 target gene, Bcl-2, and sensitized cellular toxicity induced by H(2)O(2) and etoposide. Our data indicate that MGO affects cell viability via desensitization of gp130/STAT3 signaling, which is the key signaling pathway for cell survival, and thereby promotes cytotoxicity.
Assuntos
Neuroglia/efeitos dos fármacos , Aldeído Pirúvico/farmacologia , Animais , Antineoplásicos Fitogênicos/farmacologia , Sobrevivência Celular , Células Cultivadas , Receptor gp130 de Citocina/metabolismo , Relação Dose-Resposta a Droga , Etoposídeo/farmacologia , Citometria de Fluxo , Peróxido de Hidrogênio/farmacologia , Interleucina-6/farmacologia , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/fisiologia , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Transporte Proteico/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT3/metabolismo , Nervo Isquiático/citologia , Transdução de Sinais/efeitos dos fármacos , Sais de Tetrazólio , Tiazóis , Fatores de Tempo , Transfecção/métodosRESUMO
Netrins are secreted molecules and involved in axon guidance, cell migration and tumor development. Recent studies revealed that netrins perform novel functions in such processes as epithelial development and angiogenesis without operating through the classical netrin receptors, DCC (Deleted in Colorectal Cancer) and Unc5h. In the present study, we investigated the roles of netrin-1 and its receptors in cell spreading of human glioblastoma cells, and found that netrin-1 haptotactically enhanced fibronectin-induced cell spreading and focal adhesion formation in U373 glioblastoma cells. Netrin-1 binding to the U373 cell membrane was blocked by an antibody against alphav integrin subunit, but not by an anti-DCC or anti-Unc5h antibody. In addition, enhancement of the fibronectin response by netrin-1 was abrogated by a function blocking antibody against integrin alphavbeta3. Since the alphav subunit of the integrin family plays an important role in the pathophysiological aspects of cell migration, including tumor angiogenesis and metastasis, our data provide important insight into the molecular mechanism of netrin function.
RESUMO
Although the interaction between gp130 and the ErbB family has frequently been shown in cancer cells, the mechanism of this interaction remains unclear and controversial. In the present study, we found that specific tyrphostin inhibitors of ErbB2 (AG825 and AG879), but not ErbB1 inhibitor (AG1478), suppressed IL-6-induced tyrosine phosphorylation of STAT3 in schwannoma cells. However, biochemical evidence for transactivation of ErbB2 by IL-6 was not observed. Additionally, the inhibition of ErbB2 expression, with either a specific RNAi or transfection of an ErbB2 mutant lacking the intracellular domain did not inhibit the IL-6-induced tyrosine phosphorylation of STAT3. Thus, it seems that tyrphostins, which are known as specific inhibitors of the ErbB2 kinase, may have non-specific suppressive effects on the IL-6/STAT3 pathway.
RESUMO
Netrin and its receptors, DCC (Deleted in Colorectal Cancer) and Unc5, are proposed to be involved in the axon guidance and neuroglial migration during development. However, accumulating evidence implies that they may also participate in the cell survival and apoptosis. Here, we show that netrin-1 induces proliferation of Schwann cells. Unc5b is the sole receptor expressed in RT4 schwannoma cells and adult primary Schwann cells, and netrin-1 and Unc5b are found to be expressed in the injured sciatic nerve. It was also found that the netrin-1-induced Schwann cell proliferation was blocked by the specific inhibition of Unc5b expression with RNAi. These data suggest that netrin-1 could be an endogenous trophic factor for Schwann cells in the injured peripheral nerves.
Assuntos
Fatores de Crescimento Neural/administração & dosagem , Receptores de Superfície Celular/metabolismo , Células de Schwann/metabolismo , Neuropatia Ciática/metabolismo , Proteínas Supressoras de Tumor/administração & dosagem , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Netrina-1 , Ratos , Ratos Sprague-Dawley , Células de Schwann/efeitos dos fármacos , Células de Schwann/patologia , Neuropatia Ciática/patologiaRESUMO
Netrin is a neuronal guidance molecule implicated in the development of spinal commissural neurons and cortical neurons. The attractive function of netrin requires the receptor, Deleted in Colorectal Cancer (DCC), while the receptor Unc5h is involved in the repulsive action of netrin during embryonic development. Although the expression of netrin and its receptor has been demonstrated in the adult nervous system, the function of netrin in adult neurons has not yet been elucidated. Here, we show that netrin treatment inhibited neurite outgrowth of adult dorsal root ganglion (DRG) neurons in explant and dissociated cultures. In addition, unc5h1-3 mRNAs, but not the dcc mRNA, are abundantly expressed in the adult DRG. An in situ hybridization study demonstrated that unc5h mRNAs were expressed in DRG neurons. This finding indicates that netrin/Unc5h signaling may play a role in the neurite outgrowth of adult DRG neurons and that netrin may be involved in the regulation of peripheral nerve regeneration.
Assuntos
Axônios/efeitos dos fármacos , Fatores de Crescimento Neural/farmacologia , Neurônios/efeitos dos fármacos , Proteínas Supressoras de Tumor/farmacologia , Animais , Axônios/fisiologia , Células Cultivadas , Gânglios Espinais/citologia , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Expressão Gênica/efeitos dos fármacos , Hibridização In Situ , Masculino , Regeneração Nervosa/efeitos dos fármacos , Receptores de Netrina , Netrina-1 , Neuritos/efeitos dos fármacos , Neuritos/fisiologia , Neurônios/metabolismo , Neurônios/fisiologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Superfície Celular/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Tempo , Técnicas de Cultura de TecidosRESUMO
Schwann cells provide a favorable microenvironment for successful regeneration of the injured peripheral nerve. Even though the roles of extracellular matrix proteins in the Schwann cell physiology have long been studied, the precise function of nidogen, a ubiquitous component of the basal lamina, in Schwann cells is unknown. In this study, we show that the protein and mRNA messages for nidogens are up-regulated in the sciatic nerve after sciatic nerve transection. We demonstrate that recombinant nidogen-1 increased the process formation of Schwann cells cultured from adult rat sciatic nerves and that nidogen-1 prevented Schwann cells from serum-deprivation-induced death. In addition, nidogen-1 promoted spontaneous migration of Schwann cells in two-independent migration assays. The Schwann cell responses to the recombinant nidogen-1 were specific because the nidogen-binding ectodomain of tumor endothelial marker 7 inhibited the nidogen responses without affecting Schwann cell response to laminin. Finally, we found that beta1 subunit-containing integrins play a key role in the nidogen-induced process formation, survival, and migration of Schwann cells. Altogether, these results indicate that nidogen has a prosurvival and promigratory activity on Schwann cells in the peripheral nerve.
Assuntos
Movimento Celular/efeitos dos fármacos , Glicoproteínas de Membrana/farmacologia , Bainha de Mielina/efeitos dos fármacos , Regeneração Nervosa/efeitos dos fármacos , Nervos Periféricos/efeitos dos fármacos , Células de Schwann/efeitos dos fármacos , Animais , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Movimento Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Meios de Cultura Livres de Soro/farmacologia , Integrina beta1/metabolismo , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Bainha de Mielina/fisiologia , Proteínas de Neoplasias/farmacologia , Regeneração Nervosa/fisiologia , Nervos Periféricos/citologia , Nervos Periféricos/fisiologia , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/metabolismo , Doenças do Sistema Nervoso Periférico/fisiopatologia , Estrutura Terciária de Proteína/fisiologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Superfície Celular , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes de Fusão/farmacologia , Células de Schwann/fisiologia , Neuropatia Ciática/genética , Neuropatia Ciática/metabolismo , Regulação para Cima/fisiologiaRESUMO
UNC5A-D are transmembrane receptors for netrin that plays an important role in the development of the spinal cord. However, their function in the adult nervous system remains to be established. In the present study, the mRNA expression of UNC5 family was investigated in the adult rat spinal cord following a dorsal hemisection injury. Reverse transcription-polymerase chain reaction (RT-PCR) revealed that mRNA expression of rat UNC5 family was down-regulated in the spinal cord within 3 days after the dorsal hemisection. Unc5b-d mRNA expressions returned to near normal level after a week, whereas the down-regulation of Unc5a mRNA expression was maintained until 1 month after the injury. In situ hybridization and immunofluorescent showed that both neurons and non-neuronal cells express Unc5a and b mRNAs in the adult spinal cord, and the significant long lasting down-regulation of Unc5a mRNA expression was also noticed following the spinal cord injury. This result suggests netrin/UNC5 involvement in the injury response of the adult spinal cord of the rats.
Assuntos
Regulação para Baixo/fisiologia , Receptores de Superfície Celular/metabolismo , Traumatismos da Medula Espinal/metabolismo , Animais , Hibridização In Situ/métodos , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Fatores de TempoRESUMO
Tumor endothelial marker7 (TEM7) is a transmembrane protein that is highly expressed in the tumor endothelium and neurons. In the present study, the expression profile of TEM7 mRNA and protein was investigated in the dorsal root ganglion (DRG) of the rats. In situ hybridization and reverse transcription polymerase chain reaction studies revealed that TEM7 mRNA expression was localized to the neuronal population of the sensory ganglion. Immunohistochemical analysis on TEM protein with specific antibodies further supported the spatial expression patterns of TEM7 mRNA in the DRG. The temporal expression of TEM7 mRNA in the DRG demonstrated a postnatal increase of TEM7 mRNA expression. Our results indicate that TEM7 may play a role in the peripheral sensory neurons of the vertebrate nervous systems.
Assuntos
Gânglios Espinais/citologia , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Expressão Gênica/fisiologia , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Animais , Animais Recém-Nascidos , Embrião de Mamíferos , Imuno-Histoquímica/métodos , Hibridização In Situ/métodos , Masculino , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodosRESUMO
Tumor endothelial marker 7 (TEM7) is a novel transmembrane protein that is highly expressed in the tumor endothelium. However, the ligands and functions of TEM7 are unknown at present. Using a recombinant ectodomain of TEM7 as a probe, we could identify the saturable interaction between nidogen and TEM7 in vitro. A cell overlay binding assay showed that recombinant nidogen interact with full length TEM7 on cell surface. Finally, nidogen/TEM7 interaction enhanced cell spreading in TEM7 transfected 293T cells. This novel nidogen/TEM7 interaction may provide an important molecular tool with potential therapeutic applications in the anti-angiogenic therapies.
Assuntos
Biomarcadores Tumorais/genética , Glicoproteínas de Membrana/genética , Proteínas de Neoplasias/genética , Neoplasias/genética , Receptores de Superfície Celular/genética , Biomarcadores Tumorais/metabolismo , Adesão Celular/genética , Linhagem Celular , Humanos , Ligantes , Glicoproteínas de Membrana/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias/irrigação sanguínea , Neoplasias/metabolismo , Ligação Proteica , Estrutura Terciária de Proteína/genética , Receptores de Superfície Celular/metabolismoRESUMO
The proper regulation of temporal and spatial expression of the axon guidance cues and their receptors is critical for the normal wiring of nervous system during development. Netrins, a family of secreted guidance cues, are involved in the midline crossing of spinal commissural axons and in the guidance of cortical efferents. Axons normally lose the responsiveness to their attractants when they arrive at their targets, where the attractant is produced. However the molecular mechanism is still unknown. We investigated the molecular mechanism of down-regulation of netrin-1 signaling in the embryonic cortical neurons. Netrin-1 induced the ubiquitination and proteolytic cleavage of Deleted in Colorectal Cancer (DCC), a transmembrane receptor for netrin, in dissociated cortical neurons. A dramatic decrease of DCC level particularly on the cell surface was also observed after netrin-1 stimulation. Specific ubiquitin-proteasome inhibitors prevented the netrin-induced DCC cleavage and decrease of cell surface DCC. We suggest that the ligand-mediated down-regulation of DCC might participate in the loss of netrin-responsiveness in the developing nervous system.
Assuntos
Moléculas de Adesão Celular/metabolismo , Córtex Cerebral/embriologia , Regulação para Baixo , Fatores de Crescimento Neural/farmacologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Proteínas Supressoras de Tumor/farmacologia , Ubiquitina/metabolismo , Animais , Moléculas de Adesão Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Células Cultivadas , Receptor DCC , Embrião de Mamíferos/citologia , Embrião de Mamíferos/metabolismo , Humanos , Netrina-1 , Neurônios/metabolismo , Peptídeo Hidrolases/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Superfície Celular , Proteínas Supressoras de Tumor/efeitos dos fármacosRESUMO
Tumor endothelial marker7 (TEM7) is a putative transmembrane protein that is highly expressed in the tumor endothelium. In the present study, the expression profile of TEM7 was investigated in TEM7-transfected human embryonic kidney (HEK) 293 cells and the rat brain. The extracellular secretion of the recombinant N-terminal ectodomain of TEM7, not full-length TEM7, was observed in the transiently transfected HEK 293 cells. The full-length TEM7 was found inside and membrane part of cells as demonstrated by confocal microscopy. In situ hybridization study revealed that TEM7 mRNA expressions were localized to specific neuronal areas, such as cerebellar Purkinje cells, the layer IV and V of cerebral cortex, hippocampal pyramidal cells and hypothalamic magnocellular nuclei. Immunohistochemical investigation of TEM expression with specific antibodies against TEM7 further supported the spatial expression patterns of TEM7 mRNA. The temporal expression of TEM7 mRNA in the cerebellar Purkinje cells demonstrated a postnatal developmental regulation of TEM7 expression. Our results indicate that TEM7 plays a role as a transmembrane receptor in some neuronal populations of the vertebrate brains.