scholarly journals Inhibition of mink lung epithelial cell proliferation by transforming growth factor-β is coupled through a pertussis-toxin-sensitive substrate

1990 ◽  
Vol 266 (2) ◽  
pp. 537-543 ◽  
Author(s):  
P H Howe ◽  
M R Cunningham ◽  
E B Leof
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Growth Inhibition ◽  
G Protein ◽  
Pertussis Toxin ◽  
Transforming Growth Factor ◽  
Chemical Mutagenesis ◽  
Type I ◽  
Tgf Beta ◽  
Lung Epithelial

Transforming growth factor beta 1 (TGF beta 1) inhibits the proliferative response of mink lung epithelial cells (CCL64) to serum and to epidermal growth factor (EGF). This response to TGF beta 1 can be inhibited by prior exposure of the cells to nanogram concentrations of pertussis toxin (PT), suggesting the involvement of a guanine-nucleotide-binding regulatory protein (G-protein) in mediating TGF beta 1-induced growth inhibition. To characterize further this G-protein dependence, we have isolated, by chemical mutagenesis, a CCL64 variant (CCL64-D1) that is resistant to TGF beta 1. Whereas in the parental CCL64 cells TGF beta 1 stimulates both GTP[35S] (guanosine 5′-[gamma-[35S]thio]triphosphate) binding and GTPase activity, in the CCL64-D1 variants TGF beta 1 is without effect. Quantitative immunoblotting with antisera for G-protein alpha- and beta-subunits, as well as PT-catalysed ADP-ribosylation analyses, revealed no appreciable changes in the level of G-protein expression in the CCL64-D1 variants compared with parental cells. In contrast with another TGF beta-resistant clone, MLE-M, which we show lacks detectable type I receptor protein, the CCL64-D1 cells retain all three TGF beta cell-surface binding proteins. On the basis of these studies, we propose that a necessary component of TGF beta 1-mediated growth inhibition in CCL64 epithelial cells is the coupling of TGF beta 1 receptor binding to G-protein activation.

scholarly journals Regulation of fibroblast procollagen production. Transforming growth factor-β1 induces prostaglandin E2 but not procollagen synthesis via a pertussis toxin-sensitive G-protein

1995 ◽  
Vol 307 (1) ◽  
pp. 63-68 ◽  
Author(s):  
R J McAnulty ◽  
R C Chambers ◽  
G J Laurent
Keyword(s):  
Growth Factor ◽  
Prostaglandin E2 ◽  
G Protein ◽  
Pertussis Toxin ◽  
Transforming Growth Factor ◽  
Pge2 Production ◽  
Lung Fibroblasts ◽  
Extracellular Matrix Protein ◽  
Dependent Manner ◽  
Tgf Beta

Transforming growth factor-beta 1 (TGF beta 1) initiates a series of signalling events resulting in diverse cellular responses including stimulation of extracellular matrix protein production. In this study we have investigated the role of pertussis toxin-sensitive G-proteins in mediating the effects of TGF beta 1 on fibroblast procollagen metabolism. TGF beta 1 stimulated human fetal lung fibroblast procollagen synthesis and production in a dose-dependent manner which was maximal at 0.5 ng/ml. TGF beta 1 also decreased the proportion of newly synthesized procollagen degraded intracellularly. Pertussis toxin, a G-protein inhibitor, further stimulated TGF beta 1-induced procollagen synthesis and production, but alone it had no effect on fibroblast procollagen metabolism. Addition of indomethacin also potentiated the TGF beta 1-induced increase in procollagen synthesis and production. The effects of pertussis toxin and indomethacin were not additive. Pertussis toxin and indomethacin did not affect the proportion of newly synthesized procollagen degraded intracellularly, either alone or in combination, by control cells. The TGF beta 1-induced decrease in intracellular procollagen degradation was maintained but not further affected by pertussis toxin or indomethacin. TGF beta 1 increased prostaglandin E2 (PGE2) compared with PGE2 production by control cells. Addition of pertussis toxin or indomethacin blocked the TGF beta 1-induced increase in PGE2 production. The TGF beta 1-induced increase in PGE2 preceded the increase in procollagen production. These results demonstrate that TGF beta 1-induced procollagen synthesis by lung fibroblasts is modulated by production of PGE2. Pertussis toxin and indomethacin block the production of PGE2 and enhance the effect of TGF beta 1 on procollagen synthesis. From these data we conclude that the effects of TGF beta 1 on PGE2 production but not procollagen synthesis are mediated via a receptor linked to a pertussis toxin-sensitive G-protein.

Laryngeal keratinocytes show variable inhibition of replication by TGF-beta

1990 ◽  
Vol 96 (1) ◽  
pp. 115-119
Author(s):  
T.P. DiLorenzo ◽  
B.M. Steinberg
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Growth Inhibition ◽  
Cell Density ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Marked Variation ◽  
Tgf Beta ◽  
High Calcium ◽  
Growth Factor Beta

The response of secondary human laryngeal epithelial cells to transforming growth factor-beta (TGF-beta) was investigated, and this response was compared with that of epithelial cells derived from virally induced laryngeal papillomas. In most cases, both normal laryngeal epithelial cells and those derived from laryngeal papillomas exhibited growth inhibition in response to 10 ng ml-1 TGF-beta. Response was not a function of cell density or proliferation rate when cells were in a low-calcium medium, but was reduced in high calcium. Using keratinocytes derived from several different tissue explants, we found that cells grown from different explants show marked variation in response to TGF-beta.

scholarly journals Mechanisms of Transforming Growth Factor-β Receptor Endocytosis and Intracellular Sorting Differ between Fibroblasts and Epithelial Cells

2001 ◽  
Vol 12 (3) ◽  
pp. 675-684 ◽  
Author(s):  
Jules J.E. Doré ◽  
Diying Yao ◽  
Maryanne Edens ◽  
Nandor Garamszegi ◽  
Elizabeth L. Sholl ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Ligand Binding ◽  
Transforming Growth Factor ◽  
Point Mutations ◽  
Type I ◽  
Receptor Complex ◽  
Type Ii ◽  
Down Regulation ◽  
Β Receptor

Transforming growth factor-βs (TGF-β) are multifunctional proteins capable of either stimulating or inhibiting mitosis, depending on the cell type. These diverse cellular responses are caused by stimulating a single receptor complex composed of type I and type II receptors. Using a chimeric receptor model where the granulocyte/monocyte colony-stimulating factor receptor ligand binding domains are fused to the transmembrane and cytoplasmic signaling domains of the TGF-β type I and II receptors, we wished to describe the role(s) of specific amino acid residues in regulating ligand-mediated endocytosis and signaling in fibroblasts and epithelial cells. Specific point mutations were introduced at Y182, T200, and Y249 of the type I receptor and K277 and P525 of the type II receptor. Mutation of either Y182 or Y249, residues within two putative consensus tyrosine-based internalization motifs, had no effect on endocytosis or signaling. This is in contrast to mutation of T200 to valine, which resulted in ablation of signaling in both cell types, while only abolishing receptor down-regulation in fibroblasts. Moreover, in the absence of ligand, both fibroblasts and epithelial cells constitutively internalize and recycle the TGF-β receptor complex back to the plasma membrane. The data indicate fundamental differences between mesenchymal and epithelial cells in endocytic sorting and suggest that ligand binding diverts heteromeric receptors from the default recycling pool to a pathway mediating receptor down-regulation and signaling.

scholarly journals Autocrine Transforming Growth Factor-β1 Activation Mediated by Integrin αVβ3 Regulates Transcriptional Expression of Laminin-332 in Madin-Darby Canine Kidney Epithelial Cells

2010 ◽  
Vol 21 (21) ◽  
pp. 3654-3668 ◽  
Author(s):  
Jose V. Moyano ◽  
Patricia G. Greciano ◽  
Mary M. Buschmann ◽  
Manuel Koch ◽  
Karl S. Matlin
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Transforming Growth Factor ◽  
Integrin Αvβ3 ◽  
Type I ◽  
Madin Darby Canine Kidney ◽  
Epithelial Regeneration ◽  
Tgf Β1 ◽  
Darby Canine Kidney ◽  
Canine Kidney

Laminin (LM)-332 is an extracellular matrix protein that plays a structural role in normal tissues and is also important in facilitating recovery of epithelia from injury. We have shown that expression of LM-332 is up-regulated during renal epithelial regeneration after ischemic injury, but the molecular signals that control expression are unknown. Here, we demonstrate that in Madin-Darby canine kidney (MDCK) epithelial cells LM-332 expression occurs only in subconfluent cultures and is turned-off after a polarized epithelium has formed. Addition of active transforming growth factor (TGF)-β1 to confluent MDCK monolayers is sufficient to induce transcription of the LM α3 gene and LM-332 protein expression via the TGF-β type I receptor (TβR-I) and the Smad2–Smad4 complex. Significantly, we show that expression of LM-332 in MDCK cells is an autocrine response to endogenous TGF-β1 secretion and activation mediated by integrin αVβ3 because neutralizing antibodies block LM-332 production in subconfluent cells. In confluent cells, latent TGF-β1 is secreted apically, whereas TβR-I and integrin αVβ3 are localized basolaterally. Disruption of the epithelial barrier by mechanical injury activates TGF-β1, leading to LM-332 expression. Together, our data suggest a novel mechanism for triggering the production of LM-332 after epithelial injury.

Cloning of a growth arrest-specific and transforming growth factor beta-regulated gene, TI 1, from an epithelial cell line

1991 ◽  
Vol 11 (10) ◽  
pp. 5338-5345
Author(s):  
B Kallin ◽  
R de Martin ◽  
T Etzold ◽  
V Sorrentino ◽  
L Philipson
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Lung Epithelial Cells ◽  
Epithelial Cell Line ◽  
Type I ◽  
Tgf Beta ◽  
Protein Synthesis Inhibitors ◽  
Plasminogen Activator Inhibitor 1 ◽  
Growth Factor Beta

By cDNA cloning and differential screening, five genes that are regulated by transforming growth factor beta (TGF beta) in mink lung epithelial cells were identified. A novel membrane protein gene, TI 1, was identified which was downregulated by TGF beta and serum in quiescent cells. In actively growing cells, the TI 1 gene is rapidly and transiently induced by TGF beta, and it is overexpressed in the presence of protein synthesis inhibitors. It appears to be related to a family of transmembrane glycoproteins that are expressed on lymphocytes and tumor cells. The four other genes were all induced by TGF beta and correspond to the genes of collagen alpha type I, fibronectin, plasminogen activator inhibitor 1, and the monocyte chemotactic cell-activating factor (JE gene) previously shown to be TGF beta regulated.

scholarly journals Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor beta.

1987 ◽  
Vol 165 (1) ◽  
pp. 251-256 ◽  
Author(s):  
A E Postlethwaite ◽  
J Keski-Oja ◽  
H L Moses ◽  
A H Kang
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Human Fibroblasts ◽  
Critical Role ◽  
Dermal Fibroblasts ◽  
Type I ◽  
Tgf Beta ◽  
Chemotactic Migration ◽  
Growth Factor Beta

Transforming growth factor beta (TGF-beta) is a potent chemoattractant in vitro for human dermal fibroblasts. Intact disulfide and perhaps the dimeric structure of TGF-beta is essential for its ability to stimulate chemotactic migration of fibroblasts, since reduction with 2-ME results in a marked loss of its potency as a chemoattractant. Although epidermal growth factor (EGF) appears to be capable of modulating some effects of TGF-beta, it does not alter the chemotactic response of fibroblasts to TGF-beta. Specific polyvalent rabbit antibodies to homogeneously pure TGF-beta block its chemotactic activity but has no effect on the other chemoattractants tested (platelet-derived growth factor, fibronectin, and denatured type I collagen). Since TGF-beta is secreted by a variety of neoplastic and normal cells including platelets, monocytes/macrophages, and lymphocytes, it may play a critical role in vivo in embryogenesis, host response to tumors, and the repair response that follows damage to tissues by immune and nonimmune reactions.

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