Role of platelet-derived growth factor-B, vascular endothelial growth factor, insulin-like growth factor-II, mitogen-activated protein kinase and transforming growth factor-β1 in expansion-induced lung growth in fetal sheep

2006 ◽  
Vol 18 (6) ◽  
pp. 655 ◽  
Author(s):  
Megan J. Wallace ◽  
Alison M. Thiel ◽  
Andrea M. Lines ◽  
Graeme R. Polglase ◽  
Foula Sozo ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Mapk Pathway ◽  
Fetal Lung ◽  
Mitogen Activated Protein Kinase ◽  
Insulin Like Growth Factor ◽  
Lung Expansion ◽  
Mitogen Activated Protein ◽  
Extracellular Matrix Remodelling ◽  
Tgf Β1

Increased fetal lung expansion induces lung growth, cell differentiation and extracellular matrix remodelling, although the mechanisms involved are unknown. Platelet-derived growth factor (PDGF)-B, vascular endothelial growth factor (VEGF) and insulin-like growth factor (IGF)-II are mitogens activating the mitogen-activated protein kinase (MAPK) pathway, whereas transforming growth factor (TGF)-β1 induces differentiation and extracellular matrix remodelling. In the present study, we investigated the mRNA levels of PDGF-B, VEGF, IGF-II and TGF-β1, as well as active MAPK levels, during increased fetal lung expansion induced by tracheal obstruction (TO) in sheep for 0 (controls), 36 h or 2, 4, or 10 days (n = 5 in each group). The 3.7-kb VEGF transcript increased by 30% (P < 0.05) at 36 h TO. The expression of PDGF-B decreased by approximately 25% (P < 0.01) at 2–10 days TO. In contrast, TGF-β1 mRNA increased by 96% (P < 0.05) at 10 days TO, when bioactive TGF-β1 decreased by 55% (P < 0.05). Insulin-like growth factor-II mRNA tended to increase at 10 days TO (37% above controls; P = 0.07), whereas mRNA for its receptor, IGF1R, was reduced by TO. There was no change in active MAPK levels preceding or at the time of a TO-induced 800% increase in cell proliferation. We conclude that VEGF is likely to promote expansion-induced endothelial cell proliferation, but the mechanisms underlying expansion-induced proliferation of fibroblasts and alveolar epithelial cells are unlikely to be mediated by increases in PDGF-B or IGF-II expression or activation of the MAPK pathway.

scholarly journals JNK and p38 Inhibitors Prevent Transforming Growth Factor-β1-Induced Myofibroblast Transdifferentiation in Human Graves’ Orbital Fibroblasts

2021 ◽  
Vol 22 (6) ◽  
pp. 2952
Author(s):  
Tzu-Yu Hou ◽  
Shi-Bei Wu ◽  
Hui-Chuan Kau ◽  
Chieh-Chih Tsai
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Mapk Pathway ◽  
Transforming Growth Factor Β1 ◽  
Tissue Growth ◽  
Mitogen Activated Protein Kinase ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Western Blots ◽  
Orbital Fibroblasts ◽  
Tgf Β1

Transforming growth factor-β1 (TGF-β1)-induced myofibroblast transdifferentiation from orbital fibroblasts is known to dominate tissue remodeling and fibrosis in Graves’ ophthalmopathy (GO). However, the signaling pathways through which TGF-β1 activates Graves’ orbital fibroblasts remain unclear. This study investigated the role of the mitogen-activated protein kinase (MAPK) pathway in TGF-β1-induced myofibroblast transdifferentiation in human Graves’ orbital fibroblasts. The MAPK pathway was assessed by measuring the phosphorylation of p38, c-Jun N-terminal kinase (JNK), and extracellular-signal-regulated kinase (ERK) by Western blots. The expression of connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), and fibronectin representing fibrogenesis was estimated. The activities of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) responsible for extracellular matrix (ECM) metabolism were analyzed. Specific pharmacologic kinase inhibitors were used to confirm the involvement of the MAPK pathway. After treatment with TGF-β1, the phosphorylation levels of p38 and JNK, but not ERK, were increased. CTGF, α-SMA, and fibronectin, as well as TIMP-1 and TIMP-3, were upregulated, whereas the activities of MMP-2/-9 were inhibited. The effects of TGF-β1 on the expression of these factors were eliminated by p38 and JNK inhibitors. The results suggested that TGF-β1 could induce myofibroblast transdifferentiation in human Graves’ orbital fibroblasts through the p38 and JNK pathways.

scholarly journals Role of proteins in MAPK pathways on Cleft Lip Patients of Protomalayid Race in East Nusa Tenggara Province, Indonesia

2021 ◽  
Vol 1 (1) ◽  
pp. 15-25
Author(s):  
Herman Y. L. Wihastyoko ◽  
Emilia T. Shantikaratri
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Cleft Lip ◽  
Transforming Growth Factor ◽  
Mapk Pathway ◽  
Pearson Correlation ◽  
Negative Relationship ◽  
Growth Factor Receptor ◽  
Mitogen Activated Protein Kinase ◽  
Tgf Β1

Cleft lip is a disruption which happens in the upper lip joining process due to multifactorial causes such as genetic, nutritional, environmental, and socio-economic. East Nusa Tenggara is a province in Indonesia with Protomalayid race population that has a high incidence of cleft lip of 5-6 per 1000 births. This study therefore aims to determine the expression and relationship of proteins in the Mitogen-activated Protein Kinase (MAPK) pathway of cleft lip in the Protomalayid race of East Nusa Tenggara Province. The method used was Hematoxylin-Eosin staining and Immunohistochemical technique to identify the expression of Transforming Growth Factor Alpha (TGF-α) protein, Extracellular signal-regulated kinases (ERK1), Activator Protein (AP-1), Transforming Growth Factor Beta-1 (TGF-β1), p38, Soluble Vascular Endothelial Growth Factor Receptor 1 (sVEGFR1), Epidermal Growth Factor Receptor (EGFR), and Fibroblast Growth Factor 2 (FGF- 2) in cleft lip cells. The result shows that the expressions of TGF-α, EGFR, FGF-2, and ERK-1 decreased, but that of AP-1, TGF-β1, p38, and SVEGFR1 increased. Meanwhile, the results of the Pearson correlation analysis showed the TGFα-ERK1, TGFβ1-p38, AP1-p38, EGFR-ERK1, and FGF2-p38 had a positive relationship. All the factors in the study have correlations (except FGF2 - ERK1). The relationship between FGF2-ERK1 was not significant, while SVEGFR1- p38 protein has a negative relationship.

scholarly journals Transforming growth factor β 1 inhibits mitogen-activated protein kinase induced by basic fibroblast growth factor in smooth muscle cells

1996 ◽  
Vol 316 (1) ◽  
pp. 167-173 ◽  
Author(s):  
Eliane BERROU ◽  
Michaëla FONTENAY-ROUPIE ◽  
Rozenn QUARCK ◽  
Fergus R. McKENZIE ◽  
Sylviane LÉVY-TOLEDANO ◽  
...  
Keyword(s):  
Growth Factor ◽  
Map Kinase ◽  
Kinase Activity ◽  
Transforming Growth Factor ◽  
Mitogen Activated Protein Kinase ◽  
Map Kinase Cascade ◽  
Mitogen Activated Protein ◽  
Kinase Cascade ◽  
Tgf Β1

Stimulation of smooth muscle cells with basic fibroblast growth factor (bFGF) results in the activation of the mitogen-activated protein kinase (MAP kinase) cascade and leads to cell proliferation. We show that transforming growth factor β1 (TGF-β1), at concentrations that completely inhibited bFGF-induced mitogenic activity, decreased bFGF-induced MAP kinase activity. Under these conditions, tyrosine and threonine phosphorylations of MAP kinase were differentially affected depending on the time period of TGF-β1 pretreatment. After a short (30 min) TGF-β1 pretreatment, the bFGF-mediated increase in phosphorylation of p42mapk on threonine was inhibited, with no effect on the level of phosphotyrosine or decrease in the electrophoretic mobility of p42mapk. This suggests that TGF-β1 inhibited MAP kinase activity through the action of a serine/threonine phosphatase. In contrast, a longer TGF-β1 pretreatment (4 h) partly inhibited the bFGF-induced MAP kinase mobility shift and correlated with the inhibition of phosphorylation on both threonine and tyrosine, suggesting that long-term TGF-β1 treatment prevented activation of the MAP kinase cascade or directly blocked MAP kinase. The ability of long-term (4 h) but not short-term (30 min) TGF-β1 pretreatment to inhibit MAP kinase activity was completely dependent on protein synthesis and suggests that TGF-β1 inhibits MAP kinase activity by two distinct mechanisms. These findings provide a molecular basis for the growth-inhibitory action of TGF-β1 on bFGF-induced mitogenic activity.

scholarly journals MEK1/2 Inhibitors Block Basal and Transforming Growth Factor β1-Stimulated JC Virus Multiplication

2007 ◽  
Vol 81 (12) ◽  
pp. 6412-6418 ◽  
Author(s):  
Veerasamy Ravichandran ◽  
Peter N. Jensen ◽  
Eugene O. Major
Keyword(s):  
Growth Factor ◽  
Protein Kinase ◽  
Transforming Growth Factor ◽  
Jc Virus ◽  
Transforming Growth Factor Β1 ◽  
Virus Multiplication ◽  
Membrane Receptors ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Tgf Β1

ABSTRACT The multiplication of the human neurotropic polyomavirus JC virus (JCV) is regulated by cell membrane receptors and nuclear transcription factors. Signaling pathways also play a role in determining the extent to which JCV can productively infect cells. These data show that constitutively active MEK1 protein (CA-MEK1), overexpressed in cultures of human glia, supports a substantial increase in late JCV protein (Vp-1) synthesis. The specificity of this pathway was indicated by no significant enhancement of JCV multiplication through activation of other components of mitogen-activated protein kinase pathways such as p38, Jun N-terminal protein kinase, and protein kinase A. Further evidence supporting the importance of signaling in JCV infection came from addition of transforming growth factor β1 (TGF-β1), which stimulated a 200% increase of Vp-1 expression. Specific MEK1/2 inhibitors, flavenoid PD98059 and U0126, decreased the basal and TGF-β1-stimulated Vp-1 expression by 95% or more. TGF-β1 is known to phosphorylate/activate Smad DNA binding proteins that could subsequently bind or increase binding to JCV promoter sequences, linking the effects of signaling with JCV transcriptional regulation. The effectiveness with which MEK1/2 inhibitors block JCV multiplication provides insight that may contribute to development of compounds directed against JCV.

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