An intermediary role of proHB-EGF shedding in growth factor-inducedc-Myc gene expression

2007 ◽  
Vol 214 (2) ◽  
pp. 465-473 ◽  
Author(s):  
Daisuke Nanba ◽  
Hirofumi Inoue ◽  
Yuka Shigemi ◽  
Yuji Shirakata ◽  
Koji Hashimoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Myc Gene ◽  
Intermediary Role

Growth factor-deprived BALB/c 3T3 murine fibroblasts can enter the S phase after induction of c-myc gene expression

1987 ◽  
Vol 7 (10) ◽  
pp. 3554-3560
Author(s):  
F Cavalieri ◽  
M Goldfarb
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Dna Synthesis ◽  
S Phase ◽  
3T3 Cells ◽  
Glucocorticoid Treatment ◽  
Plasmid Construct ◽  
Murine Fibroblasts ◽  
Myc Gene

Induction of quiescent BALB/c 3T3 murine fibroblasts by platelet-derived growth factor (PDGF) or fibroblast growth factor (FGFs) is accompanied by induction of c-myc gene expression. To study the role of c-myc in cell growth, we transfected BALB/c 3T3 cells with a plasmid construct containing a glucocorticoid-inducible c-myc gene. When these transfected cells were growth arrested in PDGF-FGF-freedefined medium, glucocorticoid treatment induced S-phase DNA synthesis. This induction of DNA synthesis was inefficient, and cell proliferation was not evident, suggesting that growth factors act through stimulation of c-myc expression together with other intracellular events.

scholarly journals Growth factor-deprived BALB/c 3T3 murine fibroblasts can enter the S phase after induction of c-myc gene expression.

1987 ◽  
Vol 7 (10) ◽  
pp. 3554-3560 ◽  
Author(s):  
F Cavalieri ◽  
M Goldfarb
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Dna Synthesis ◽  
S Phase ◽  
3T3 Cells ◽  
Glucocorticoid Treatment ◽  
Plasmid Construct ◽  
Murine Fibroblasts ◽  
Myc Gene

Induction of quiescent BALB/c 3T3 murine fibroblasts by platelet-derived growth factor (PDGF) or fibroblast growth factor (FGFs) is accompanied by induction of c-myc gene expression. To study the role of c-myc in cell growth, we transfected BALB/c 3T3 cells with a plasmid construct containing a glucocorticoid-inducible c-myc gene. When these transfected cells were growth arrested in PDGF-FGF-freedefined medium, glucocorticoid treatment induced S-phase DNA synthesis. This induction of DNA synthesis was inefficient, and cell proliferation was not evident, suggesting that growth factors act through stimulation of c-myc expression together with other intracellular events.

P–181 Morphine regulates BMP4 growth factor and is involved in in-vitro early embryo development and PGCs formation

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
I Muñoa ◽  
M Araolaza-Lasa ◽  
I Urizar-Arenaza ◽  
M Gianzo Citores ◽  
N Subiran Ciudad
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Environmental Factors ◽  
Embryo Development ◽  
Early Embryo ◽  
Epigenetic Changes ◽  
Morphine Treatment ◽  
Early Embryo Development

Abstract Study question To elucidate if morphine can alter embryo development. Summary answer Chronic morphine treatment regulates BMP4 growth factor, in terms of gene expression and H3K27me3 enrichment and promotes in-vitro blastocysts development and PGC formation. What is known already BMP4 is a member of the bone morphogenetic protein family, which acts mainly through SMAD dependent pathway, to play an important role in early embryo development. Indeed, BMP4 enhances pluripotency in mouse embryonic stem cells (mESCs) and, specifically, is involved in blastocysts formation and primordial germ cells (PGCs) generation. Although, external morphine influence has been previously reported on the early embryo development, focus on implantation and uterus function, there is a big concern in understanding how environmental factors can cause stable epigenetic changes, which could be maintained during development and lead to health problems. Study design, size, duration First, OCT4-reported mESCs were chronically treated with morphine during 24h, 10–5mM. After morphine removal, mESCs were collected for RNA-seq and H3K27me3 ChIP-seq study. To elucidate the role of morphine in early embryo development, two cell- embryos stage were chronically treated with morphine for 24h and in-vitro cultured up to the blastocyst stage in the absence of morphine. Furthermore, after morphine treatment mESCs were differentiated to PGCs, to elucidate the role of morphine in PGC differentiation. Participants/materials, setting, methods Transcriptomic analyses and H3K27me3 genome wide distribution were carried out by RNA-Sequencing and Chip-Sequencing respectively. Validations were performed by RNA-RT-qPCR and Chip-RT-qPCR. Main results and the role of chance Dynamic transcriptional analyses identified a total of 932 differentially expressed genes (DEGs) after morphine treatment on mESCs, providing strong evidence of a transcriptional epigenetic effect induced by morphine. High-throughput screening approaches showed up Bmp4 as one of the main morphine targets on mESCs. Morphine caused an up-regulation of Bmp4 gene expression together with a decrease of H3K27me3 enrichment at promoter level. However, no significant differences were observed on gene expression and H3K27me3 enrichment on BMP4 signaling pathway components (such as Smad1, Smad4, Smad5, Smad7, Prdm1 and Prmd14) after morphine treatment. On the other hand, the Bmp4 gene expression was also up-regulated in in-vitro morphine treated blastocyst and in-vitro morphine treated PGCs. These results were consistent with the increase in blastocyst rate and PGC transformation rate observed after morphine chronic treatment. Limitations, reasons for caution To perform the in-vitro analysis. Further studies are needed to describe the whole signaling pathways underlying BMP4 epigenetic regulation after morphine treatment. Wider implications of the findings: Our findings confirmed that mESCs and two-cell embryos are able to memorize morphine exposure and promote both blastocyst development and PGCs formation through potentially BMP4 epigenetic regulation. These results provide insights understanding how environmental factors can cause epigenetic changes during the embryo development, leading to alterations and producing health problems/diseases Trial registration number Not applicable

scholarly journals Dual Role for Transforming Growth Factor β-Dependent Signaling in Trypanosoma cruzi Infection of Mammalian Cells

2000 ◽  
Vol 68 (4) ◽  
pp. 2077-2081 ◽  
Author(s):  
Belinda S. Hall ◽  
Miercio A. Pereira
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Trypanosoma Cruzi ◽  
Host Cell ◽  
Cell Lines ◽  
Mammalian Cells ◽  
Transforming Growth Factor ◽  
Growth Arrest ◽  
Transforming Growth Factor Β

ABSTRACT Expression of functional transforming growth factor β (TGF-β) receptors (TβR) is required for the invasion of mammalian cells by the protozoan parasite Trypanosoma cruzi. However, the precise role of this host cell signaling complex in T. cruzi infection is unknown. To investigate the role of the TGF-β signaling pathway, infection levels were studied in the mink lung epithelial cell lines JD1, JM2, and JM3. These cells express inducible mutant TβR1 proteins that cannot induce growth arrest in response to TGF-β but still transmit the signal for TGF-β-dependent gene expression. In the absence of mutant receptor expression, trypomastigotes invaded the cells at a low level. Induction of the mutant receptors caused an increase in infection in all three cell lines, showing that the requirement for TGF-β signaling at invasion can be divorced from TGF-β-induced growth arrest. TGF-β pretreatment of mink lung cells expressing wild-type TβR1 caused a marked enhancement of infection, but no enhancement was seen in JD1, JM2, and JM3 cells, showing that the ability of TGF-β to stimulate infection is associated with growth arrest. Likewise, expression of SMAD7 or SMAD2SA, inhibitors of TGF-β signaling, did not block infection by T. cruzi but did block the enhancement of infection by TGF-β. Taken together, these results show that there is a dual role for TGF-β signaling in T. cruzi infection. The initial invasion of the host cell is independent of both TGF-β-dependent gene expression and growth arrest, but TGF-β stimulation of infection requires a fully functional TGF-β signaling pathway.

Thrombospondin-1 (TSP1) Promotes Thrombin Generation on the Surface of Fibroblasts (HS-68) and Induces Up-Regulation of Connective Tissue Growth Factor (CTGF) Gene and Protein Expression.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1755-1755 ◽  
Author(s):  
Joanne Manns ◽  
Mario Rico ◽  
Leonard L. Mason ◽  
De La Cadena A. Raul
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Protein Expression ◽  
Thrombin Generation ◽  
Human Fibroblasts ◽  
Inhibitory Effect ◽  
Factor V ◽  
Prothrombinase Complex ◽  
Gene And Protein Expression

Abstract TSP1 has the ability to bind to human fibroblasts, to form a complex with coagulation factor V/Va (Thrombosis Research 116:533, 2005), to promote thrombin generation on the surface of a monocytic cell line and to neutralize tissue factor pathway inhibitor (TFPI) (J Biol Chem275:31715, 2000). Disruption of TSP1 binding to neutrophils was associated with beneficial effects in an experimental animal model of inflammation, in part, by down regulating CTGF gene and protein expression (Arthritis Rheum54:2415, 2006). CTGF is a novel potent cysteine-rich heparin-binding growth factor and is highly expressed by fibroblasts. CTGF plays a major role in angiogenesis and fibrosis. There is also growing evidence that CTGF may be the downstream autocrine mediator responsible for some of the cellular effects of TGF-beta. Since fibroblasts express tissue factor (TF) on their surface, and purified thrombin and TF-VIIa complex have been shown to up-regulate the gene expression of CTGF (J Biol Chem275:14632, 2000) experiments were conducted to evaluate the ability of HS-68 to support assembly of the prothrombinase complex, TF-FVIIa, thrombin generation and the effect of thrombin generation on CTGF expression. The role of TSP1 in these reactions was assessed as well. Thrombin generation was measured by the chromogenic substrate S-2238. Although the initial rates of the reactions are available we are presenting the end-point values of the reaction expressed in umol/L of pNA released per minute. All reaction mixtures were performed in the presence of 2mM Ca++. When HS-68 cells were preincubated with FVII (5 nM) prior to the addition of activated factor V (FVa, 45nM)), FX (5nM) and prothrombin (FII, 1.4 uM), thrombin was efficiently generated (282 umol/L pNA/min), indicating that FVII was activated by TF expressed by the cell and that the HS-68 cell membrane provided an ideal surface for the reaction to occur. The addition of FII, FV, FVII and FX to the reaction mixtures was an absolute requirement. When the reaction mixture was evaluated in the presence of FII, FV, FVII, FX and TFPI (8nM), there was a 70% reduction in thrombin production (86 umol/L pNA released) confirming the important role of TFPI in regulating the activity of the TF-FVIIa complex. The addition of TSP1 to the reaction mixture containing FII, FV, FVII and FX at concentrations found in plasma during the inflammatory response (20nM) enhanced the production of thrombin (327 umol/L pNA released per min) and neutralized the inhibitory effect of TFPI by 50% (171 umol/L pNA released per min). Therefore, TSP1 promotes thrombin generation by participating in the assembly of the prothrombinase complex on the surface of HS-68 cells and by neutralizing, in part, the inhibitory effect of TFPI on TF-VIIa complex. Finally, thrombin generation on the surface of HS-68 cells was associated with up-regulation of CTGF gene expression from the baseline value by 67% at 1hr and 72% by 2 hrs. In summary, we have identified on human fibroblasts a pathway previously shown to play an important role on human neutrophils and in an experimental model of inflammation. Our laboratory is currently characterizing the binding of TSP1 to this cell line and silencing the gene for TSP1 to test its potential therapeutic benefit in an experimental model of erosive arthritis and to further determine the role of TSP1 in this pathway.

scholarly journals Nuclear Factor I-C Links Platelet-Derived Growth Factor and Transforming Growth Factor β1 Signaling to Skin Wound Healing Progression

2009 ◽  
Vol 29 (22) ◽  
pp. 6006-6017 ◽  
Author(s):  
Genta Plasari ◽  
Alessandra Calabrese ◽  
Yves Dusserre ◽  
Richard M. Gronostajski ◽  
Alan Mcnair ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Wound Closure ◽  
Transforming Growth Factor ◽  
Platelet Derived Growth Factor ◽  
Nuclear Factor ◽  
Matrix Deposition ◽  
Factor I ◽  
Nuclear Factor I

ABSTRACT Transforming growth factor β (TGF-β) and platelet-derived growth factor A (PDGFΑ) play a central role in tissue morphogenesis and repair, but their interplay remain poorly understood. The nuclear factor I C (NFI-C) transcription factor has been implicated in TGF-β signaling, extracellular matrix deposition, and skin appendage pathologies, but a potential role in skin morphogenesis or healing had not been assessed. To evaluate this possibility, we performed a global gene expression analysis in NFI-C−/− and wild-type embryonic primary murine fibroblasts. This indicated that NFI-C acts mostly to repress gene expression in response to TGF-β1. Misregulated genes were prominently overrepresented by regulators of connective tissue inflammation and repair. In vivo skin healing revealed a faster inflammatory stage and wound closure in NFI-C−/− mice. Expression of PDGFA and PDGF-receptor alpha were increased in wounds of NFI-C−/− mice, explaining the early recruitment of macrophages and fibroblasts. Differentiation of fibroblasts to contractile myofibroblasts was also elevated, providing a rationale for faster wound closure. Taken together with the role of TGF-β in myofibroblast differentiation, our results imply a central role of NFI-C in the interplay of the two signaling pathways and in regulation of the progression of tissue regeneration.

Role of growth factors in acute lung injury induced by paraquat in a rat model

2010 ◽  
Vol 30 (6) ◽  
pp. 460-469 ◽  
Author(s):  
Xiangdong Jian ◽  
Ming Li ◽  
Yijing Zhang ◽  
Yanjun Ruan ◽  
Guangran Guo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Lung Injury ◽  
Growth Factors ◽  
Growth Factor ◽  
Lung Injury ◽  
Rat Model ◽  
Transforming Growth Factor ◽  
Pcr Analysis ◽  
Circulatory Level

Paraquat (PQ) can cause acute lung injury in humans and experimental animals. However, the role of growth factors in the progression of injury has not been clearly established. We developed an animal model of PQ-induced lung injury using Wistar rats. One milliliter of PQ solution (30, 60, and 120 mg/kg) was applied through the lavage, while the same amount of vehicle was applied to control rats. Based on histopathology, the lungs of some animals exposed to PQ showed acute fulmination, resulting in death, while others showed a more protracted injury, resulting in typical pulmonary fibrosis at 21 days. Using this PQ-poisoned rat model, we examined the intrapulmonary gene expression and circulatory level of cytokines and growth factors at 8 hours, 24 hours, 3 days, 7 days, 14 days, and 21 days after PQ administration. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated that the gene expression levels of interleukin-1 beta and interleukin-6 were significantly increased at 21 days after PQ challenge compared with the controls. The mRNA expression of tumor necrosis factor-alpha was also significantly increased except on days 14 and 21 after PQ treatment. Moreover, PQ-treated rats showed enhanced gene expression of growth factors such as platelet-derived growth factor-A and insulin-like growth factor-1 at 21 days and transforming growth factor-beta 1 at 14 days. ELISA results showed the circulatory level of cytokines and growth factors coincided with intrapulmonary gene expression. The synergistic effects of these molecules are presumed to cause pulmonary damage due to PQ challenge and may become targets of treatment.

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