Página 1 dos resultados de 2728 itens digitais encontrados em 0.011 segundos

TGF-beta and CD23 are involved in nitric oxide production by pulmonary macrophages activated by beta-glucan from Paracoccidioides brasiliensis

QUEIROZ JR., Luiz de Padua; MATTOS JR., Marden Estevao; SILVA, Marcelo Fernandes da; SILVA, Celio Lopes
Fonte: SPRINGER Publicador: SPRINGER
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
66.46%
Pulmonary macrophages (PM), which are CD11b/CD18(+) and CD23(+), may be involved in the onset of inflammatory events caused by Paracoccidioides brasiliensis in the lungs. In the present study, we measured the nitric oxide (NO) and interleukin in PM production after intratracheal (i.t.) inoculation of an enriched beta-glucan cell wall fraction from P. brasiliensis (Fraction F1). BALB/c and C57/BL6 (B6) mice were i.t. treated with Fraction F1, and their PM were restimulated in vitro with LPS and interferon-gamma up to 14 days after treatment. Macrophages BALB/c mice produced less NO than PM from B6 mice. The lower NO production was caused by higher production of TGF-beta by pulmonary macrophages of BALB/c and was abrogated by anti-TGF-beta MoAb in vitro and in vivo. Other interleukins such as IL-10, IL-4 and a combination of IL-1, TNF-alpha and IL-6 were not involved in NO production induced by Fraction F1. Expression of CD11b increases and expression of CD23 decreases on PM of BALB/c mice after in vivo treatment whereas PM of B6 mice do not show a variation of their phenotype. Moreover, the ability of pulmonary macrophages to induce lymphocyte proliferation was reduced in mixed cultures of CD11b(+) or CD23(+) macrophages but was restored when lymphocytes were cultivated in the presence of NO inhibitor (L-NMMA). Thus...

Mast cells, TGF-beta 1 and alpha-SMA expression in IgA nephropathy

SILVA, G. E. B.; COSTA, R. S.; RAVINAL, R. C.; REIS, M. A. dos; DANTAS, M.; COIMBRA, T. M.
Fonte: IOS PRESS Publicador: IOS PRESS
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
66.49%
IgA nephropathy (IgAN) is a kidney disease with a varying renal prognosis. Recently, many studies have demonstrated that renal alpha-smooth muscle actin (alpha-SMA) and transforming growth factor (TGF-beta 1) expression, as well interstitial mast cell infiltrates could represent a prognostic marker in several renal diseases. The aim of our study was to analyze the prognostic value of mast cell, TGF-beta 1 and alpha-SMA expression in IgAN. A survey of the medical records and renal biopsy reports of 62 patients with a diagnosis of IgAN followed-up from 1987 to 2003 was performed. The mean follow-up time was 74.7 +/- 50.0 months. The immunohistochemical studies were performed using a monoclonal antibody anti-human mast cell tryptase, a polyclonal antibody anti-human TGF-beta 1, and a monoclonal antibody anti-human alpha-SMA. An unfavorable clinical course of IgAN was related to interstitial mast cell infiltrates and alpha-SMA expression in the tubulointerstitial area. Expression of glomerular TGF-beta 1 and alpha-SMA, and interstitial TGF-beta 1 is not correlated with clinical course in IgAN. In conclusion, the increased number of mast cells and higher alpha-SMA expression in the tubulointerstitial area may be predictive factors for the poor prognosis of patients with IgAN.

Developing human minor salivary glands: morphological parallel relation between the expression of TGF-beta isoforms and cytoskeletal markers of glandular maturation

LOURENCO, Silvia Vanessa; UYEKITA, Sabrina Hitomi; LIMA, Dirce Mary Correia; SOARES, Fernando Augusto
Fonte: SPRINGER Publicador: SPRINGER
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
66.52%
Morphogenesis of salivary glands involves complex coordinated events. Synchronisation between cell proliferation, polarisation and differentiation, which are dependent on epithelial-mesenchymal interactions and on the microenvironment, is a requirement. Growth factors mediate many of these orchestrated biological processes and transforming growth factor-beta (TGF-beta) appear to be relevant. Using immunohistochemistry and immunofluorescence, we have mapped the distribution of TGF-beta 1, 2 and 3 and compared it with the expression of maturation markers in human salivary glands obtained from foetuses ranging from weeks 4 to 24 of gestation. TGF-beta 1 first appeared during canalisation stage in the surrounding mesenchyme and, in the more differentiated stages, was expressed in the cytoplasm of acinar cells throughout the adult gland. TGF-beta 2 was detected since the bud stage of the salivary gland. Its expression was observed in ductal cells and increased along gland differentiation, TGF-beta 3 was detected from the canalisation stage of the salivary gland, being weakly expressed on ductal cells, and it was the only factor detected on myoepithelial cells. The data suggest that TGF-beta have a role to play in salivary gland development and differentiation.

Expression of transforming growth factor-beta 1, -beta 2, and -beta 3 in human developing teeth: Immunolocalization according to the odontogenesis phases

BENEDETE, Ana Paula Sassa; SOBRAL, Ana Paula Veras; LIMA, Dirce Mary Correia; KAMIBEPPU, Leonardo; SOARES, Fernando Augusto; LOURENCO, Silvia Vanessa
Fonte: ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS Publicador: ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
56.57%
Transforming growth factor-beta (TGF-beta) is a multifunctional growth factor that has several biological effects in vivo including control of cell growth and differentiation, cell migration, lineage determination, motility, adhesion, apoptosis, and synthesis and degradation of extracellular matrix, and TGF-beta plays an important role in regulating tissue repair and regeneration. Our study analyzed the participation of TGF-beta 1, -beta 2, and -beta 3 in the different stages of morphogenesis and differentiation of human developing dental organ using immunobistochemistry. The maxillae and mandibles of 10 human embryos ranging from 8 to 23 weeks of gestation were employed, according to the approval of the ethical committee. Our study revealed that the TGF-beta subunits-beta 1, beta 2, and beta 3 were present in the various stages of tooth development, but the expression varied according to the differentiation stage, tissue, and TGF-beta subunit. Our results indicated that TGF-beta 1 is closely related to differentiation of enamel organ and initiation of matrix secretion, TGF-beta 2 to cellular differentiation, and TGF-beta 3 to mineral maturation matrix.

In vivo effects of TGF beta 1 on the the growth of gastric epithelium in suckling rats

SA, Eunice Ribeiro de Andrade; BITENCOURT, Blanca; ALVARES, Eliana Parisi; GAMA, Patricia
Fonte: ELSEVIER SCIENCE BV Publicador: ELSEVIER SCIENCE BV
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
66.57%
As the content of Transforming Growth Factor-beta (TGF beta) wanes in the milk of lactating rat, an increase in TGF beta is observed in the gastric epithelia concomitant with differentiation of the glands upon weaning. Whereas TGF beta has been shown to inhibit the proliferation of gastrointestinal cells in vitro, its functional significance and mechanisms of action have not been studied in vivo. Therefore, we administered TGF beta 1 (1 ng/g body wt.) to 14-day-old rats in which the gastric epithelium was induced to proliferate by fasting, and determined the involvement of signaling through Smads and the impact on epithelial cell proliferation and apoptosis. After the gavage, we observed the progressive increase of active TGF beta 1 while T beta RII-receptor remained constant in the gastric mucosa. By immunohistochemistry, we showed Smad2/3 increase at 60 min (p < 0.05) and Smad2 phosphorylation/activation and translocation to the nucleus most prominently between 0 and 30 min after treatment (p < 0.05). Importantly, TGF beta 1 inhibited cell proliferation (p < 0.05), which was estimated by BrDU pulse-labeling 12 h after gavage. Lower proliferation was reflected by increased p27(kip1) at 2 h (p < 0.05). Also, TGF beta 1 increased apoptosis as measured by M30 labeling at 60 and 180 min (p < 0.001)...

Bradykinin B(1) receptor antagonist R954 inhibits eosinophil activation/proliferation/migration and increases TGF-beta and VEGF in a murine model of asthma

VASQUEZ-PINTO, Luciana M. C.; NANTEL, Francois; SIROIS, Pierre; JANCAR, Sonia
Fonte: CHURCHILL LIVINGSTONE Publicador: CHURCHILL LIVINGSTONE
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
66.4%
In the present study the effects of bradykinin receptor antagonists were investigated in a murine model of asthma using BALB/c mice immunized with ovalbumin/alum and challenged twice with aerosolized ovalbumin. Twenty four hours later eosinophil proliferation in the bone marrow, activation (lipid bodies formation), migration to lung parenchyma and airways and the contents of the pro-angiogenic and pro-fibrotic cytokines TGF-beta and VEGF were determined. The antagonists of the constitutive B(2) (HOE 140) and inducible B(1) (R954) receptors were administered intraperitoneally 30 min before each challenge. In sensitized mice, the antigen challenge induced eosinophil proliferation in the bone marrow, their migration into the lungs and increased the number of lipid bodies in these cells. These events were reduced by treatment of the mice with the B(1) receptor antagonist. The B(2) antagonist increased the number of eosinophils and lipid bodies in the airways without affecting eosinophil counts in the other compartments. After challenge the airway levels of VEGF and TGF-beta significantly increased and the B(1) receptor antagonist caused a further increase. By immunohistochemistry techniques TGF-beta was found to be expressed in the muscular layer of small blood vessels and VEGF in bronchial epithelial cells. The B(1) receptors were expressed in the endothelial cells. These results showed that in a murine model of asthma the B(1) receptor antagonist has an inhibitory effect on eosinophils in selected compartments and increases the production of cytokines involved in tissue repair. It remains to be determined whether this effects of the B(1) antagonist would modify the progression of the allergic inflammation towards resolution or rather towards fibrosis. (C) 2009 Elsevier Ltd. All rights reserved.

Effect of human TGF-beta on the gene expression profile of Schistosoma mansoni adult worms

Oliveira, Katia C.; Carvalho, Mariana L. P.; Verjovski-Almeida, Sergio; LoVerde, Philip T.
Fonte: ELSEVIER SCIENCE BV; AMSTERDAM Publicador: ELSEVIER SCIENCE BV; AMSTERDAM
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
66.39%
Schistosoma mansoni is responsible for schistosomiasis, a parasitic disease that affects 200 million people worldwide. Molecular mechanisms of host-parasite interaction are complex and involve a crosstalk between host signals and parasite receptors. TGF-beta signaling pathway has been shown to play an important role in S. mansoni development and embryogenesis. In particular human (h) TGF-beta has been shown to bind to a S. mansoni receptor, transduce a signal that regulates the expression of a schistosome target gene. Here we describe 381 parasite genes whose expression levels are affected by in vitro treatment with hTGF-beta. Among these differentially expressed genes we highlight genes related to morphology, development and cell cycle that could be players of cytokine effects on the parasite. We confirm by qPCR the expression changes detected with microarrays for 5 out of 7 selected genes. We also highlight a set of non-coding RNAs transcribed from the same loci of protein-coding genes that are differentially expressed upon hTCF-beta treatment. These datasets offer potential targets to be explored in order to understand the molecular mechanisms behind the possible role of hTGF-beta effects on parasite biology. (C) 2012 Elsevier B.V. All rights reserved.; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP); Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP); NIH [AI 46762]; NIH; CNPq; CNPq; NIAID; NIAID [HHSN272201000009I]

TGF-beta 1 modulates the homeostasis between MMPs and MMP inhibitors through p38 MAPK and ERK1/2 in highly invasive breast cancer cells

Gomes, Luciana Rodrigues; Terra, Letícia Ferreira; Mansano, Rosangela Aparecida Wailemann; Labriola, Leticia; Sogayar, Mari Cleide
Fonte: BIOMED CENTRAL LTD; LONDON Publicador: BIOMED CENTRAL LTD; LONDON
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
66.59%
Background: Metastasis is the main factor responsible for death in breast cancer patients. Matrix metalloproteinases (MMPs) and their inhibitors, known as tissue inhibitors of MMPs (TIMPs), and the membrane-associated MMP inhibitor (RECK), are essential for the metastatic process. We have previously shown a positive correlation between MMPs and their inhibitors expression during breast cancer progression; however, the molecular mechanisms underlying this coordinate regulation remain unknown. In this report, we investigated whether TGF-beta 1 could be a common regulator for MMPs, TIMPs and RECK in human breast cancer cell models. Methods: The mRNA expression levels of TGF-beta isoforms and their receptors were analyzed by qRT-PCR in a panel of five human breast cancer cell lines displaying different degrees of invasiveness and metastatic potential. The highly invasive MDA-MB-231 cell line was treated with different concentrations of recombinant TGF-beta 1 and also with pharmacological inhibitors of p38 MAPK and ERK1/2. The migratory and invasive potential of these treated cells were examined in vitro by transwell assays. Results: In general, TGF-beta 2, T beta RI and T beta RII are over-expressed in more aggressive cells, except for T beta RI...

Expressão de genes homeobox em células de carcinoma epidermóide de boca estimuladas com EGF e TGF-beta; Expression of homeobox genes in oral squamous cell carcinoma cell lines, stimulated with EGF and TGF-beta

Campos, Marcia Sampaio
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 21/01/2008 Português
Relevância na Pesquisa
66.49%
Genes homeobox, vitais para muitos aspectos relacionados com crescimento e diferenciação celular, têm sido descritos desregulados em alguns cânceres. Seu papel na carcinogênese, principalmente de carcinomas epidermóides de boca, permanence pouco claro e pobremente caracterizado. Desse modo, esse estudo objetivou avaliar, em cultura de células, o perfil de expressão de seis genes homeobox (ASH2L, HOXA7, HHEX, PKNOX1, PITX1, TGIF) selecionados dentre aqueles previamente identificados no Projeto Genoma Câncer de Cabeça e Pescoço (2001) sob estímulo de EGF e TGF-beta1. Para tal, linhagens celulares de carcinoma epidermóide de cabeça e pescoço primário (HN6) e metastático (HN31) e uma linhagem não-tumoral (HaCat) foram cultivadas sob condições-padrão. Após a confecção dos cDNAs de cada linhagem, por meio de RT-PCR, os transcritos foram amplificados e quantificados pela técnica de PCR em tempo real. Os dados foram normalizados com o gene HPRT e a quantificação relativa foi realizada seguindo o método do delta Ct. De acordo com os resultados foi possível verificar que o EGF produziu uma modulação variável da expressão dos genes avaliados em todas as linhagens celulares, enquanto que, em geral, o TGF-beta1 foi capaz de aumentar significantemente (ANOVA...

Aspectos moleculares do efeito do fator de transformação de crescimento-beta1 (TGF-β1) nas vias de sinalização na biomineralização in vitro.; Molecular aspects of the effect of transforming growth factor-beta 1 (TGF-β1) in the signaling pathways in vitro biomineralization.

Donato, Tatiani Ayako Goto
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 11/03/2014 Português
Relevância na Pesquisa
66.63%
Este estudo in vitro teve como objetivo avaliar os efeitos moleculares do TGF-β1, com diferentes períodos de suplementação, sobre a formação do fenótipo osteogênico das células MC3T3-E1, comparando-os com células tratadas com AA+β-GP suplementados com Dex e/ou TGF-β1, sem e com a neutralização dos receptores de TGF-β1. A expressão gênica do próprio TGF-β1 e Smad3 foram analisadas, bem como, a diferenciação das células osteogênicas e a biomineralização. As células tratadas com TGF-β1 sem neutralização de receptores apresentam efeito inibitório nos estágios mais avançados da diferenciação dos osteoblastos e da biomineralização in vitro, mas expressarem alguns marcadores importantes envolvidos na mineralização. Observaram-se nódulos de mineral em todos os tratamentos das células que tiveram os receptores de TGF-β1 neutralizados, mas houve uma diminuição na expressão de alguns genes. Os resultados confirmam a complexidade da via de sinalização do TGF-β1, mostrando que existem lacunas para que seja entendido o mecanismo dessa molécula na biologia osteoblástica.; This in vitro study aimed to evaluate the molecular effects of TGF-β1, with different supplementation time periods on the establishment of MC3T3-E1 cells...

Platelet aggregation and TGF-beta(1) plasma levels in pregnant women with preeclampsia

Peracoli, Maria Terezinha Serrão; Menegon, Fernanda Tereza Ferreira; Borges, Vera Therezinha Medeiros; Costa, Roberto Antonio de Araújo; Thomazini-Santos, Izolete Aparecida; Peraçoli, José Carlos
Fonte: Elsevier B.V. Publicador: Elsevier B.V.
Tipo: Artigo de Revista Científica Formato: 79-84
Português
Relevância na Pesquisa
66.54%
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Processo FAPESP: 02/09590-0; Objectives: Platelets and transforming growth factor-beta(1) (TGF-beta(1)) are thought to be involved in the pathogenesis of preeclampsia. Our objectives were to determine plasma concentration of TGF-beta(1) in normotensive and preeclamptic women in the third trimester of pregnancy and to evaluate the correlation of TGF-beta(1) plasma levels with platelet count and agonist-induced aggregation capacity.Methods: Thirty-three women with preeclampsia were compared with 36 healthy women with uncomplicated pregnancies. Peripheral venous blood samples were obtained, and TGF-beta(1) plasma levels measured by an enzyme-linked immunoassay. Platelet aggregation was induced by the agonist agents adenosine diphosphate (ADP), collagen and epinephrine, and was determined in platelet-rich plasma by aggregometry.Results: Plasma concentrations of active TGF-beta(1) were significantly higher in preeclamptic women (10.41 +/- 2.07 ng/mL) compared with normotensive pregnant women (7.01 +/- 3.29 ng/mL). Platelet number and platelet agonist-induced aggregation percent were significantly lower in patients with precclampsia than in healthy pregnant women. A significant correlation was observed between TGF-beta(1) plasma levels and platelet agonist-induced aggregation percent as between plasma levels of TGF-beta(1) and platelet number in preeclamptic patients.Conclusion: The association between impairment in platelet responsiveness and higher levels of TGF-beta(1) in the plasma of patients with preeclampsia suggests that this cytokine may play a role in the pathophysiological events of preeclampsia that are dependent on platelet activation. (C) 2008 Elsevier B.V. All rights reserved.

Absence of transforming growth factor-beta type II receptor is associated with poorer prognosis in HER2-negative breast tumours

Paiva, C. E.; Drigo, S. A.; Rosa, F. E.; Neto, F. A. Moraes; Caldeira, Jose R. F.; Soares, F. A.; Domingues, M. A. C.; Rogatto, Silvia Regina
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica Formato: 734-740
Português
Relevância na Pesquisa
56.61%
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq); Processo FAPESP: 07/52632-0; Background: The clinical relevance of transforming growth factor-beta (TGF-beta)-signalling pathway in breast carcinomas (BCs) remained elusive. This study aimed to evaluate the prognostic value of TGF-beta and transforming growth factor-beta type II receptor (TGF-beta RII) expression levels in tumour cells and their association with the established biomarkers in BC.Patients and methods: In 324 BC from patients with long-term follow-up, the TGF-beta 1 and TGF-beta RII transcript and protein expression levels were assessed.Results: TGF-beta 1 and TGF-beta RII down-expression was significantly associated with BC. Negative TGF-beta 1 and TGF-beta RII protein status was associated with the development of distant metastasis (P = 0.003 and P = 0.029, respectively). In multivariate analysis, TGF-beta 1-positive tumours were associated with increased disease-free survival (DFS) [hazard ratio (HR) = 0.489, P = 0.003]. TGF-beta RII positivity was an independent prognostic factor for DFS (HR = 0.439, P = 0.001) and overall survival (OS) (HR = 0.409, P = 0.003) in human epidermal growth factor receptor2 (HER2)-negative patients. Absence of TGF-beta 1 and TGF-beta RII proteins in breast tumour cells was significantly associated with metastasis development.Conclusions: To the best of our knowledge...

Absence of TGF-beta RII predicts bone and lung metastasis and is associated with poor prognosis in stage III breast tumors

Paiva, Carlos Eduardo; Serrano, Sergio Vicente; Ribeiro Paiva, Bianca Sakamoto; Scapulatempo-Neto, Cristovam; Soares, Fernando Augusto; Rogatto, Silvia Regina; Alencar Marques, Mariangela Esther
Fonte: IOS Press Publicador: IOS Press
Tipo: Artigo de Revista Científica Formato: 209-217
Português
Relevância na Pesquisa
66.51%
In the case of operated breast cancer (BC), prognostic markers help to determine if the patient needs additional treatment and predictive markers help the clinician to decide which treatment to use. Thus, a better knowledge of known predictive and prognostic markers and the identification of new markers, may improve the treatment of BC patients. The transforming growth factor-beta type II receptor (TGF-beta RII), a main receptor of transforming growth factor beta pathway, is a potential new prognostic marker. The aims of the present study were to investigate both the predictive and prognostic impact of TGF-beta RII in BC samples. TGF-beta RII protein expression was evaluated using immunohistochemistry on a tissue microarray containing 110 TNM stage III BC samples obtained prior to doxorubicin-based neoadjuvant chemotherapy (NAC). Our results demonstrate that TGF-beta RII did not predict the response to NAC. on the other hand, an association between TGF-beta RII-negative tumor and higher risk of metastasis to lungs and bones was verified. TGF-beta RII negativity was an independent prognostic factor for decreased disease-free and overall survival.

Expression of TGF-beta and its receptors in murine fetal and adult dermal wounds

Cowin, A.; Holmes, T.; Brosnan, P.; Ferguson, M.
Fonte: John Libbey Eurotext Ltd Publicador: John Libbey Eurotext Ltd
Tipo: Artigo de Revista Científica
Publicado em //2001 Português
Relevância na Pesquisa
66.53%
The transforming growth factor-betas (TGF-betas) are of major importance in wound healing and have been implicated in the scar-less wound repair observed in fetuses. Few studies have characterised the role of TGF-beta in fetal wound repair and to date no studies have characterised the expression of its receptors within non-scarring fetal wounds. We have localised the TGF-beta isoforms beta1, beta2 and beta3 and its two receptors, TGF-betaRI and TGF-betaRII in both adult and fetal dermal murine wounds. We observed low level immunofluorescence of TGF-beta1 and TGF-beta2 in fetal wounds and although TGF-beta3 staining was observed in the epidermis of fetal skin, there was no upregulation in response to injury. By contrast, all three isoforms were strongly expressed in adult wounds. Similar to its ligands, TGF-beta receptor expression was increased post-wounding in the adult wounds. However, in contrast, no mRNA or protein for either of the TGF-beta receptors was observed in response to wounding in the fetal dermis although there was both mRNA and protein expression of both the receptors localised within the fetal alimentary tract, one of the few fetal organs which does scar post-injury. The differences that we observed in the expression of TGF-beta and its receptors in adult and fetal wounds could be important in the absence of scar formation that is observed in the fetus.; Allison J. Cowin...

Einfluss von TGF-beta1 auf T-Zellen bei der Juvenilen Idiopathischen Arthritis; Influence of TGF-beta1 on T-cells at the Juvenile Idiopathic Arthritis

Müller, Markus
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
Relevância na Pesquisa
56.58%
Die Juvenile Idiopathische Arthritis (JIA) ist eine heterogene Gruppe entzündlicher Erkrankungen der Gelenke im Kindesalter. Grundlage der JIA ist eine Immunreaktion der Synovia, welche wahrscheinlich T-Zell vermittelt ist. Da frühere Studien gezeigt haben, dass die Wirkung von TGF-beta1 von dem Aktivierungs- und Differenzierungsstatus der Zellen abhängig ist, wurden in dieser Arbeit die isolierten T-Zellen aus peripherem Blut und Synovialflüssigkeit (SF) mittels Durchflusszytometrie phänotypisch charakterisiert. Es zeigte sich, dass es bei der JIA zu einer Anreicherung von CD8+-T-Zellen in der SF im Vergleich zum peripheren Blut kommt. Insgesamt dominierten aktivierte Gedächtniszellen (CD4+CD45RO+) bei allen Patienten. Wie in früheren Studien konnte eine starke Zunahme der Aktivierungsmarker CD69 und HLA-DR in der SF gegenüber peripherem Blut beobachtet werden. Das dabei gezeigte unterschiedliche Verhalten von CD4+- und CD8+-T-Zellen bezüglich CD69 (frühe Aktivierung) bzw. HLA-DR (als Langzeitaktivierungsmarker) könnte auf unterschiedliche Aktivierungszeitpunkte hindeuten. Auffallend war auch der höhere Anteil der als regulatorische Zellen (Tregs) bezeichneten CD4+CD25high+-T-Zellen in der SF im Vergleich zum peripheren Blut. Unterschiede zwischen der prognostisch günstigeren oligo- und der ungünstigeren polyartikulären Verlaufsform zeigten sich nicht. Bei anderen chronisch-entzündlichen Erkrankungen...

Participación de la familia de factores TGF-beta en la percepción del dolor

Lantero García, Aquilino
Fonte: Universidade de Cantabria Publicador: Universidade de Cantabria
Tipo: Tese de Doutorado
Português
Relevância na Pesquisa
66.32%
El pseudorreceptor de TGF-beta, BAMBI, se localiza en regiones del sistema nervioso relevantes en la transmisión del dolor. La ausencia de BAMBI condiciona un fenotipo hipoalgésico frente a estímulos nociceptivos agudos y retrasa el desarrollo de alodinia en un modelo de dolor neuropático. El fenotipo es revertido por antagonistas opioides, implicando al sistema opioide endógeno. A nivel presináptico, la ausencia de BAMBI incrementa la expresión de opioides endógenos y la inhibición de su degradación con RB101 potencia el fenotipo hioalgésico. el efecto analgésico de la morfina está incrementado en los ratones deficientes en BAMBI, tanto en condiciones fisiológicas como de dolor neuropático. El mecanismo neuroquímico subyacente está ligado al aumento de receptores opioides que asocia un incremento en la inhibición de la adenilatociclasa inducida por antagonistas. TGF-beta1 ejerce una acción antialodínica que es revertida por el antagonista opioide naloxona. Este efecto se asocia con un incremento de POMC y de receptores opioides mi en la médula espinal y en cultivos celulares. Concluimos que TGF-beta1 está implicado en la facilitación pre y postsináptica de la activida opioide endógena.

MicroRNA miR-146b-5p regulates signal transduction of TGF-beta by repressing SMAD4 in thyroid cancer

Geraldo, M. V.; Yamashita, A. S.; Kimura, E. T.
Fonte: NATURE PUBLISHING GROUP; LONDON Publicador: NATURE PUBLISHING GROUP; LONDON
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
66.53%
MicroRNAs (miRNA) are small non-coding RNAs involved in post-transcriptional gene regulation that have crucial roles in several types of tumors, including papillary thyroid carcinoma (PTC). miR-146b-5p is overexpressed in PTCs and is regarded as a relevant diagnostic marker for this type of cancer. A computational search revealed that miR-146b-5p putatively binds to the 3' untranslated region (UTR) of SMAD4, an important member of the transforming growth factor beta (TGF-beta) signaling pathway. The TGF-beta pathway is a negative regulator of thyroid follicular cell growth, and the mechanism by which thyroid cancer cells evade its inhibitory signal remains unclear. We questioned whether the modulation of the TGF-beta pathway by miR-146b-5p can contribute to thyroid tumorigenesis. Luciferase reporter assay confirmed the direct binding of miR-146b-5p on the SMAD4 3'UTR. Specific inhibition of miR-146b-5p with a locked nucleic acid-modified anti-miR-146b oligonucleotide significantly increased SMAD4 levels in the human papillary carcinoma cell lines, TPC-1 and BCPAP. Moreover, suppression of miR-146b-5p increased the cellular response to the TGF-beta anti-proliferative signal, significantly decreasing the proliferation rate. The overexpression of miR-146b-5p in normal rat follicular PCCL3 cells decreased SMAD4 levels and disrupted TGF-beta signal transduction. MiR-146b-5p overexpression in PCCL3 cells also significantly increased cell proliferation in the absence of thyroid-stimulating hormone and conferred resistance to TGF-beta-mediated cell-cycle arrest. Additionally...

A Mechanism and Pro-migratory Function for Non-canonical TGF-beta Signaling through Smad1 and Smad5

Liu, Irwin
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Dissertação Formato: 2807392 bytes; application/pdf
Publicado em 10/12/2008 Português
Relevância na Pesquisa
66.61%

During the course of breast cancer progression, normally dormant tumor-promoting effects of transforming growth factor-beta (TGF-beta) including migration, invasion, and metastasis are unmasked. Although this switch or gain of TGF-beta function has been modeled extensively in in-vivo and in-vitro breast cancer systems, the signaling mechanisms that control this TGF-beta switch are poorly understood. Indeed, the precise role of canonical TGF-beta signaling through the type I TGF-beta receptor, ALK5, and its intracellular effectors, Smad2 and Smad3, is still poorly understood. In an effort to identify mechanisms that regulate the ability of TGF-beta to stimulate mammary epithelial cell migration in-vitro, we found that TGF-beta stimulates the phosphorylation of Smad1 and Smad5, intracellular effectors that are typically associated with bone morphogenetic protein (BMP) signaling. As this phosphorylation response has not been reported extensively, little is known about the prevalance, mechanism, function, or pathological relevance of TGF-beta-stimulated Smad1/5 phosphorylation.

Herein, we use pharmacologic inhibition, RNA interference, and additional biochemical and cell-based approaches to identify a novel mechanism and function for non-canonical TGF-beta signaling through an ALK5-Smad1/5 axis. We show that TGF-beta stimulates Smad1/5 phosphorylation in an ALK5 dependent manner in cells of epithelial...

Role of the Type III TGF-beta Receptor Cytoplasmic Domain in Breast Cancer Progression

Lee, Jason Dole
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Dissertação Formato: 5142718 bytes; application/pdf
Publicado em //2009 Português
Relevância na Pesquisa
66.6%

Breast cancer remains among the most common cancers of the developed world. Despite advances in treatment modalities, deaths due to breast cancer are the second leading cause of cancer death among women. The transforming growth factor-beta (TGF-β) pathway is an important modulator of breast cancer progression, acting in a tumor suppressing fashion in early carcinogenesis but switching in a poorly understood fashion to a promoter of cancer progression in later stages. Mutations and loss of function of TGF-β components are common across a variety of cancers. In particular, the expression of the type III TGF-β receptor (TβRIII) is decreased with cancer grade and clinical progression in prostate, lung, ovarian, and pancreatic cancers. In an effort to enhance our understanding of the biology of TGF-β on carcinogenesis, this dissertation looks at the role of TβRIII in breast cancer progression.

Through an examination of clinical specimens, loss of TβRIII was seen at both the message and protein levels with increasing tumor grade. Analysis of correlated patient outcomes showed that low TβRIII expression was predictive of a shorter time to recurrence, demonstrating clinical relevance for TβRIII expression. The contribution of TβRIII to tumor progression was further examined by examining known TGF-β functions...

Ectodomain Shedding of TGF-beta Receptors: Role in Signaling and Breast Cancer Biology

Elderbroom, Jennifer Lynn
Fonte: Universidade Duke Publicador: Universidade Duke
Tipo: Dissertação
Publicado em //2013 Português
Relevância na Pesquisa
66.59%

The transforming growth factor beta (TGF-beta) signaling pathway is a critical regulator of multiple biological processes that are involved in cancer progression, such as proliferation, migration, invasion and metastasis. TGF-beta ligands bind to multiple high-affinity receptors (TbetaRI, TbetaRII, TbetaRIII), whose expression on the cell surface, and subsequent ability to transduce signaling, can be modulated by ectodomain shedding.

TbetaRIII, also known as betaglycan, is the most abundantly expressed TGF-beta receptor. TbetaRIII suppresses breast cancer progression through inhibiting migration, invasion, metastasis, and angiogenesis. TbetaRIII binds TGF-beta ligands, with membrane-bound TbetaRIII presenting ligand to enhance TGF-beta signaling. However, TbetaRIII can also undergo ectodomain shedding, releasing soluble TbetaRIII, which binds and sequesters ligand to inhibit downstream signaling. To investigate the relative contributions of soluble and membrane-bound TbetaRIII on TGF-beta signaling and breast cancer biology, here I describe TbetaRIII mutants with impaired (Delta-Shed-TbetaRIII) or enhanced ectodomain shedding (SS-TbetaRIII). Relative to wild-type (WT)-TbetaRIII, Delta-Shed-TbetaRIII increased TGF-beta signaling and blocked TbetaRIII's ability to inhibit breast cancer cell migration and invasion. Conversely...