RESUMO
The development of the gastric mucosa is controlled by hormones, growth factors and feeding behavior. Early weaning (EW), which means the abrupt interruption of suckling, increases proliferation and differentiation in the rat gastric epithelium. Transforming growth factor alpha (TGFalpha) is secreted in the stomach, binds to the epidermal growth factor receptor (EGFR) and may control cell proliferation, differentiation and migration. Here, we investigated the influence of suckling-weaning transition on the differentiation of mucous neck cells in the stomach and its association to the expression of TGFalpha and EGFR. Fifteen-day-old Wistar rats were divided into two groups: suckling (control), in which pups were kept with the dam, and early weaning (EW), in which rats were separated from their mother and fed with hydrated powdered chow. TGFalpha and EGFR levels were increased at 18 days in EW animals compared to control ones (p<0.05). Histochemical reactions with Periodic Acid-Schiff reagent+Alcian Blue or Bandeiraea simplicifolia II lectin were used to stain the mucous neck cells and showed an increase in this cell population throughout EW, which was more pronounced at 17 days when compared to suckling pups (p<0.05). These morphological results were confirmed by RT-PCR for mucin 6. The levels of mucin 6 mRNA were higher in EW animals from the 16th to the 18th day (1-3 days post-weaning) when compared to the respective control group. Inhibition of EGFR through AG1478 administration to EW animals prevented the expansion of mucous neck cell population induced by EW (p<0.05). Therefore, early weaning up regulated TGFalpha/EGFR expression and induced differentiation of mucous neck cells. Moreover, we showed that EGFR takes part in the maturation of this cell population. We conclude that regular suckling-weaning transition is crucial to guarantee the development of the gastric mucosa.
Assuntos
Diferenciação Celular , Receptores ErbB/fisiologia , Mucosa Gástrica/citologia , Regulação da Expressão Gênica no Desenvolvimento , Fator de Crescimento Transformador alfa/fisiologia , Animais , Western Blotting , Células Cultivadas , Receptores ErbB/antagonistas & inibidores , Feminino , Mucosa Gástrica/metabolismo , Técnicas Imunoenzimáticas , Mucina-6/genética , Quinazolinas , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tirfostinas/farmacologia , DesmameRESUMO
A pesar del progreso logrado en el campo de la biología pulpar, la técnica y la filosofía sobre el recubrimiento pulpar ha generado inmensas controversias. Los clínicos conocen bien los éxitos logrados cuando se trabaja sobre el conducto radicular, pero no están muy convencidos de los éxitos de los recubrimientos pulpares durante actos de operatoria dental. Investigaciones recientes han demostrado que exposiciones pulpares pueden curar mediante la formación de dentina adicional y así separar la pulpa del medio externo. Es sabido, hoy en día, que el pronóstico de un recubrimiento pulpar es un tema a tratar en la operatoria dental. Los elementos que pueden producir un recubrimiento pulpar satisfactorio son discutivos en conjutno con los llamados factores de crecimiento. El propósito de crear nueva dentina es primariamente motivado por la necesidad clínica de restaurar este tejido mineralizado. La dentina rodea y protege el centro vital de la pieza dentaria que reside en la pulpa dental. Este tejido se encuentra mineralizado en un 80 por ciento y provee, en combinación con el esmalte, la mayor estructura del total de la masa dentaria. Al igual que el esmalte, la dentina es un tejido avascular pero, a diferencia de este, las células que sintetiza la dentina (los odontoblastos) pueden permanecer vitales a través de la vida adulta y volver a generar dentina adicional. Recientes investigaciones han sugerido que si los odontoblastos ubicados en la matriz preodontoblástica se pierden, es posible inducir la diferenciación de nuevas células odontoblásticas formadoras del complejo dentinopulpar utilizando las denominadas proteínas morfogenéticas. Desarrollos satisfactorios de procesos de ingeniería molecular que puedan regenerar dentina pueden tener aplicaciones clínicas como un agente para recubrimiento pulpar potenciado como desensibilizante, debido al sellado de los túbulos dentinarios (AU)
Assuntos
Substâncias de Crescimento/classificação , Substâncias de Crescimento/fisiologia , Substâncias de Crescimento/uso terapêutico , Dentística Operatória/tendências , Proteínas Morfogenéticas Ósseas/fisiologia , Odontoblastos/fisiologia , Dentinogênese/fisiologia , Amelogênese/fisiologia , Capeamento da Polpa Dentária/métodos , Dentina Secundária/fisiologia , Fatores de Crescimento Transformadores/fisiologia , Fatores de Crescimento Transformadores/classificação , Fator de Crescimento Transformador beta/fisiologia , Fator de Crescimento Transformador alfa/fisiologia , Remineralização Dentária , Hidróxido de Cálcio/química , Ácido Edético/química , Dentina/anatomia & histologia , Dentina/ultraestrutura , Dentina/efeitos dos fármacosRESUMO
Like other types of pre-malignant lesions and carcinoma, angiogenesis is associated with high-grade cervical dysplasia and with invasive squamous carcinoma of the cervix. Vascular endothelial cell growth factor (VEGF) is known to be one of the most important inducers of angiogenesis and is upregulated in carcinoma of the cervix. Human Papilloma Virus 16 (HPV-16) has been etiologically linked to human cervical cancer, and the major oncogenic proteins encoded by the viral genome, E6 and E7, are involved in the immortalization of target cells. Because several oncogenes including mutant ras, EGF receptor, ErbB2/Her2, c-myc and v-src upregulate VEGF expression, we asked whether HVP-16 E6 oncoprotein could act in a similar fashion. We found that HPV-16 E6-positive cells generally express high levels of VEGF message. Furthermore, co-expression of the VEGF promoter-Luc (luciferase) reporter gene with E6 in both human keratinocytes and mouse fibroblast showed that E6 oncoprotein upregulates VEGF promoter activity, and does so in a p53 independent manner. An E6 responsive region which comprises four Sp-1 sites, between -194 and -50 bp of the VEGF promoter, is also necessary for constitutive VEGF transcription. Taken together, our results suggest the possibility that the HPV oncoprotein E6 may contribute to tumor angiogenesis by direct stimulation of the VEGF gene.
Assuntos
Fatores de Crescimento Endotelial/genética , Genes p53 , Linfocinas/genética , Neovascularização Patológica/genética , Proteínas Oncogênicas Virais/fisiologia , Papillomaviridae/genética , Regiões Promotoras Genéticas , Proteínas Repressoras , Proteína Supressora de Tumor p53/fisiologia , Comunicação Autócrina , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Fatores de Crescimento Endotelial/metabolismo , Receptores ErbB/fisiologia , Feminino , Células HeLa/metabolismo , Células HeLa/virologia , Humanos , Queratinócitos/virologia , Linfocinas/metabolismo , Proteínas de Neoplasias/fisiologia , Neovascularização Patológica/fisiopatologia , Proteínas Oncogênicas Virais/genética , Papillomaviridae/fisiologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Proteínas Recombinantes de Fusão/biossíntese , Transcrição Gênica , Ativação Transcricional , Fator de Crescimento Transformador alfa/fisiologia , Células Tumorais Cultivadas/metabolismo , Células Tumorais Cultivadas/virologia , Infecções Tumorais por Vírus/patologia , Infecções Tumorais por Vírus/virologia , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular , Neoplasias Vulvares/metabolismo , Neoplasias Vulvares/patologia , Neoplasias Vulvares/virologiaAssuntos
Humanos , Animais , Ratos , Substâncias de Crescimento/fisiologia , Cicatrização/fisiologia , Cicatriz/fisiopatologia , Substâncias de Crescimento/uso terapêutico , Fator de Crescimento Epidérmico/fisiologia , Fator de Crescimento Transformador alfa/fisiologia , Fator de Crescimento Derivado de Plaquetas/fisiologia , Fator de Crescimento Transformador beta/fisiologia , Fatores de Crescimento de Fibroblastos/fisiologia , Somatomedinas/fisiologia , Interleucinas/fisiologia , Cicatrização/efeitos dos fármacos , Suínos , Coelhos , Modelos Animais de DoençasAssuntos
Humanos , Animais , Ratos , Cicatriz/fisiopatologia , Cicatrização/fisiologia , Substâncias de Crescimento/fisiologia , Cicatrização , Modelos Animais de Doenças , Fator de Crescimento Epidérmico/fisiologia , Fatores de Crescimento de Fibroblastos/fisiologia , Substâncias de Crescimento/uso terapêutico , Interleucinas/fisiologia , Fator de Crescimento Derivado de Plaquetas/fisiologia , Coelhos , Somatomedinas/fisiologia , Suínos , Fator de Crescimento Transformador alfa/fisiologia , Fator de Crescimento Transformador beta/fisiologiaRESUMO
The liver is considered the center of the metabolism. Many of its functions are controlled by a network of mediators. Hepatic regeneration is a highly regulated event also by several substances. Herein is was reviewed the literature about the role of cytokines, prostaglandins and nitric oxide in this event. Prior, it was described the known activities of each substance in the body. Further, it was examined since the production until the action of each one in regenerating livers. We could conclude that some of these mediators present a well-defined action, while others are object of great controversy. Overall, the comprehension of the liver's regeneration is very important in concern to develop new kinds of treatment in hepatology.
Assuntos
Citocinas/fisiologia , Óxido Nítrico/fisiologia , Prostaglandinas/fisiologia , Regeneração Hepática/fisiologia , Fator de Crescimento de Hepatócito/fisiologia , Fator de Crescimento Epidérmico/fisiologia , Fatores de Crescimento de Fibroblastos/fisiologia , Interleucina-1/fisiologia , Interleucina-6/fisiologia , Fator de Crescimento Transformador alfa/fisiologia , Fator de Crescimento Transformador beta/fisiologia , Fator de Necrose Tumoral alfa/fisiologiaRESUMO
OBJECTIVE: Because the role of cytomegalovirus in Ménétrier disease in children remains unclear and recent studies have implicated transforming growth factor alpha in the pathogenesis of this disease in adults, we investigated the possibilities that (1) cytomegalovirus is etiologic in Ménétrier disease in children and (2) transforming growth factor alpha mediates its development. METHODS: The presence of a cytomegaloviral infection and the pattern of transforming growth factor alpha immunolocalization were determined in the gastric mucosa of four pediatric patients with Ménétrier disease, in control subjects (children with normal gastric mucosa, gastritis, or prostaglandin E1-induced antral hyperplasia), and in adults with Ménétrier disease. RESULTS: Evidence of a cytomegaloviral infection was present only in the four children with Ménétrier disease. The pattern of transforming growth factor alpha immunostaining was identical in the specimens from pediatric and adult patients with Ménétrier disease. This pattern was distinct from that found in the pediatric control specimens. CONCLUSIONS: These data strengthen the possibilities that cytomegalovirus is etiologic in children and that transforming growth factor alpha is involved in the pathogenesis of Ménétrier disease in both children and adults.
Assuntos
Citomegalovirus/fisiologia , Gastrite Hipertrófica/etiologia , Gastrite Hipertrófica/virologia , Fator de Crescimento Transformador alfa/fisiologia , Adulto , Pré-Escolar , Citomegalovirus/ultraestrutura , Feminino , Mucosa Gástrica/ultraestrutura , Helicobacter pylori/isolamento & purificação , Helicobacter pylori/ultraestrutura , Humanos , Lactente , Masculino , Cultura de VírusRESUMO
Multiple transforming growth factors (TGFs) capable of conferring the neoplastic phenotype on NRK-49F cells without the addition of any other exogenous growth factor in the soft agar assay, were purified from two human solid malignant neoplasms: a squamous lung carcinoma and a pectoral rhabdomyosarcoma. In both tumors, low-molecular-weight transforming activities (4000-6000) that were not potentiated by epidermal growth factor (EGF), competed for binding to the EGF receptor, possessed mitogenic activity on NRK fibroblasts arrested in serum-deprived medium, and did not show inhibitory effects on DNA synthesis induced by EGF and insulin in NRK cells. Other TGFs with molecular weights 9000 to 48,000, were also found in the malignant tissues examined; these TGFs, were not potentiated by EGF, did not compete for binding to the EGF receptor, were not mitogenic for NRK cells, and acted as potent inhibitors of DNA synthesis induced by EGF and insulin in NRK cells. These results demonstrate that growth-promoting activities, and modulating agents that can act as either enhancers or inhibitors of cell proliferation, are present in neoplastic tissues of different embryologic origin and histologic type.