scholarly journals Transforming Growth Factor Beta has Dual Effects on MMP9 and uPA Expression in HTR-8/SVneo Human Trophoblastic Cell Line

2019 ◽  
Vol 24 (1) ◽  
pp. 26-37
Author(s):  
Sandra Susana Novoa Herran ◽  
Mariela Castelblanco ◽  
Myriam Sanchez-Gomez ◽  
Adriana Umaña Pérez
Keyword(s):  
Transcription Factors ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
In Silico ◽  
Transforming Growth Factor ◽  
In Silico Analysis ◽  
Negative Regulator ◽  
Trophoblast Invasion ◽  
Trophoblastic Cell ◽  
Growth Factor Beta

Invasion of trophoblast into endometrium is vital for successful pregnancy development. MMP9 and uPA are key proteases in this process, but it is still not clear the regulation of its expression by Transforming Growth Factor Beta (TGF-β), known negative regulator of trophoblast invasion. We evaluated the effect of TGF-β on the transcriptional expression of uPA and MMP9 over time, in HTR- /SVneo trophoblast cells cultured with or without 0.5 % fetal bovine serum, via RT qPCR. The involved transcription factors and signaling pathways were analyzed in silico, using Proscan, Enrich, PCViz and WikiPathway. Results showed that that TGF-β regulates the expression of uPA and MMP9. Serum modified the nature of TGF-β’s effects on uPA expression, from negative without serum to positive with it, showing opposite effects on MMP9 expression. In silico analysis evidenced different transcription factors for each protease, some belonging to TGF-β ssignaling pathway, and crosstalk with MAPK and Wnt/β-catenin pathways. The TGF-β ddual role is discussed proposing that serum affects the cellular context. Transcriptional regulation of MMP9 and uPA by TGF-β is differential and depends on serum presence and evaluation time.

scholarly journals Descrição da frequência de variantes genéticas no gene da endoglina em uma população do Nordeste do Brasil

2018 ◽  
Vol 17 (3) ◽  
pp. 392
Author(s):  
Yasmim Cristina Ferreira de Almeida ◽  
Camila Alexandrina Figueiredo
Keyword(s):  
Latin America ◽  
Social Change ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
In Silico ◽  
Transforming Growth Factor ◽  
On Line ◽  
Asthma And Allergy ◽  
Growth Factor Beta

<p><strong>Introdução: </strong>A endoglina<strong> </strong>(ENG, CD105) é um co-receptor da família <em>transforming growth factor-beta</em> e participa da regulação de processos celulares como proliferação, diferenciação, migração e apoptose. ENG é mais conhecida por sua expressão em células endoteliais, desempenhando papel importante na angiogênese e vasculogênese, porém sua expressão já foi associada a diferentes desfechos patogênicos, inclusive devido a mutações no gene <em>ENG</em>. <strong>Objetivos: </strong>Descrever a frequência de variantes genéticas no gene <em>ENG</em>, comparar com populações ancestrais e analisar as variantes genéticas que possam estar envolvidas em processos patogênicos em outras populações.  <strong>Metodologia: </strong>Foi utilizado o banco de dados do programa SCAALA (Social Change Asthma and Allergy in Latin America) para a população do estudo, sendo genotipado 1309 indivíduos usando o chip Illumina 2.5 Human Omni Bead e feitas análises <em>in silico </em>utilizando plataformas on-line<em>.</em> <strong>Resultados: </strong>As variantes genéticas rs10987746, rs10121110, rs11792480 e rs16930129 apresentaram frequência de menor alelo entre 16 a 48% na população estudada, as quais foram mais reiteradamente próximas do padrão africano que do europeu. Os SNVs foram relacionados aos mecanismos regulatórios genéticos conhecidos, pressupondo que essas variantes não estejam envolvidas diretamente em processos funcionais. <strong>Conclusão:</strong> São necessárias maiores investigações referentes aos mecanismos funcionais deste gene, visto que a endoglina participa de uma gama de processos celulares importantes e mais esforços devem ser feitos para estudos genéticos na população brasileira, considerando a mistura de populações.</p>

Enhanced jun gene expression is an early genomic response to transforming growth factor beta stimulation

1989 ◽  
Vol 9 (3) ◽  
pp. 1255-1262
Author(s):  
L Pertovaara ◽  
L Sistonen ◽  
T J Bos ◽  
P K Vogt ◽  
J Keski-Oja ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Transcription Factors ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
A549 Cells ◽  
Base Line ◽  
Tgf Beta ◽  
Early Effect ◽  
Growth Factor Beta

Transforming growth factor beta (TGF beta) is a multifunctional polypeptide that regulates proliferation, differentiation, and other functions of many cell types. The pathway of TGF beta signal transduction in cells is unknown. We report here that an early effect of TGF beta is an enhancement of the expression of two genes encoding serum- and phorbol ester tumor promoter-regulated transcription factors: the junB gene and the c-jun proto-oncogene, respectively. This stimulation was observed in human lung adenocarcinoma A549 cells which were growth inhibited by TGF beta, AKR-2B mouse embryo fibroblasts which were growth stimulated by TGF beta, and K562 human erythroleukemia cells, which were not appreciably affected in their growth by TGF beta. The increase in jun mRNA occurred with picomolar TGF beta concentrations within 1 h of TGF beta stimulation, reached a peak between 1 and 5 h in different cells, and declined gradually to base-line levels. This mRNA response was followed by a large increase in the biosynthesis of the c-jun protein (AP-1), as shown by metabolic labeling and immunoprecipitation analysis. However, differential and cell type-specific regulation appeared to determine the timing and magnitude of the response of each jun gene in a given cell. In AKR-2B and NIH 3T3 cells, only junB was induced by TGF beta, evidently in a protein synthesis-independent fashion. The junB response to TGF beta was maintained in c-Ha-ras and neu oncogene-transformed cells. Thus, one of the earliest genomic responses to TGF beta may involve nuclear signal transduction and amplification by the junB and c-jun transcription factors in concert with c-fos, which is also induced. The differential activation of the jun genes may explain some of the pleiotropic effects of TGF beta.

scholarly journals Transforming growth factor beta inhibits the proliferation of the blast cells of acute myeloblastic leukemia

Blood ◽  
1988 ◽  
Vol 72 (1) ◽  
pp. 159-164 ◽  
Author(s):  
N Tessier ◽  
T Hoang
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Acute Myeloblastic Leukemia ◽  
Negative Regulator ◽  
Thymidine Uptake ◽  
Tgf Beta ◽  
Bladder Cell ◽  
Growth Factor Beta

Abstract The effect of transforming growth factor beta (TGF beta) on proliferation and differentiation of peripheral blast precursors in acute myeloblastic leukemia (AML) was investigated. TGF beta induced a dose-dependent inhibition of blast clonogenic cells in suspension and methylcellulose cultures in the presence of optimal concentrations of stimulators provided by conditioned media from the bladder cell line HTB9 (HTB9-CM) or the recombinant granulocyte-macrophage colony- stimulating factor (GM-CSF). On removal of TGF beta, blast clonogenic cell proliferation recovers to the same level as that observed in control cultures, indicating that the effect is reversible. There was no induction of cell differentiation, as indicated by morphological and functional studies (production of superoxyde anions). Cell cycle analysis by thymidine uptake and flow cytometry with a DNA binding dye indicated that TGF beta caused a delay in progression into S and G2/M phases of the cell cycle without affecting cell viability. Thus, TGF beta appears to have a cytostatic rather than cytolytic effect on blast precursors and might therefore play a role as a negative regulator in hematopoiesis.

scholarly journals Enhanced jun gene expression is an early genomic response to transforming growth factor beta stimulation.

1989 ◽  
Vol 9 (3) ◽  
pp. 1255-1262 ◽  
Author(s):  
L Pertovaara ◽  
L Sistonen ◽  
T J Bos ◽  
P K Vogt ◽  
J Keski-Oja ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Transcription Factors ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
A549 Cells ◽  
Base Line ◽  
Tgf Beta ◽  
Early Effect ◽  
Growth Factor Beta

Transforming growth factor beta (TGF beta) is a multifunctional polypeptide that regulates proliferation, differentiation, and other functions of many cell types. The pathway of TGF beta signal transduction in cells is unknown. We report here that an early effect of TGF beta is an enhancement of the expression of two genes encoding serum- and phorbol ester tumor promoter-regulated transcription factors: the junB gene and the c-jun proto-oncogene, respectively. This stimulation was observed in human lung adenocarcinoma A549 cells which were growth inhibited by TGF beta, AKR-2B mouse embryo fibroblasts which were growth stimulated by TGF beta, and K562 human erythroleukemia cells, which were not appreciably affected in their growth by TGF beta. The increase in jun mRNA occurred with picomolar TGF beta concentrations within 1 h of TGF beta stimulation, reached a peak between 1 and 5 h in different cells, and declined gradually to base-line levels. This mRNA response was followed by a large increase in the biosynthesis of the c-jun protein (AP-1), as shown by metabolic labeling and immunoprecipitation analysis. However, differential and cell type-specific regulation appeared to determine the timing and magnitude of the response of each jun gene in a given cell. In AKR-2B and NIH 3T3 cells, only junB was induced by TGF beta, evidently in a protein synthesis-independent fashion. The junB response to TGF beta was maintained in c-Ha-ras and neu oncogene-transformed cells. Thus, one of the earliest genomic responses to TGF beta may involve nuclear signal transduction and amplification by the junB and c-jun transcription factors in concert with c-fos, which is also induced. The differential activation of the jun genes may explain some of the pleiotropic effects of TGF beta.

scholarly journals Transforming growth factor beta inhibits the proliferation of the blast cells of acute myeloblastic leukemia

Blood ◽  
1988 ◽  
Vol 72 (1) ◽  
pp. 159-164 ◽  
Author(s):  
N Tessier ◽  
T Hoang
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Acute Myeloblastic Leukemia ◽  
Negative Regulator ◽  
Thymidine Uptake ◽  
Tgf Beta ◽  
Bladder Cell ◽  
Growth Factor Beta

The effect of transforming growth factor beta (TGF beta) on proliferation and differentiation of peripheral blast precursors in acute myeloblastic leukemia (AML) was investigated. TGF beta induced a dose-dependent inhibition of blast clonogenic cells in suspension and methylcellulose cultures in the presence of optimal concentrations of stimulators provided by conditioned media from the bladder cell line HTB9 (HTB9-CM) or the recombinant granulocyte-macrophage colony- stimulating factor (GM-CSF). On removal of TGF beta, blast clonogenic cell proliferation recovers to the same level as that observed in control cultures, indicating that the effect is reversible. There was no induction of cell differentiation, as indicated by morphological and functional studies (production of superoxyde anions). Cell cycle analysis by thymidine uptake and flow cytometry with a DNA binding dye indicated that TGF beta caused a delay in progression into S and G2/M phases of the cell cycle without affecting cell viability. Thus, TGF beta appears to have a cytostatic rather than cytolytic effect on blast precursors and might therefore play a role as a negative regulator in hematopoiesis.

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