Ovarian transforming growth factor-beta (TGF-beta) receptors: in-vitro effects of follicle stimulating hormone, epidermal growth factor and TGF-beta on receptor expression in human preantral follicles

The NF-kappa B transcription factor is a pleiotropic activator that participates in the induction of a wide variety of cellular genes. Antisense oligomer inhibition of the RelA subunit of NF-kappa B results in a block of cellular adhesion and inhibition of tumor cell growth. Investigation of the molecular basis for these effects showed that in vitro inhibition of the growth of transformed fibroblasts by relA antisense oligonucleotides can be reversed by the parental-cell-conditioned medium. Cytokine profile analysis of these cells treated with relA antisense oligonucleotides revealed inhibition of transforming growth factor beta 1 (TGF-beta 1 to the transformed fibroblasts reversed the inhibitory effects of relA antisense oligomers on soft agar colony formation and cell adhesion to the substratum. Direct inhibition of TGF-beta 1 expression by antisense phosphorothioates to TGF-beta 1 mimicked the in vitro effects of blocking cell adhesion that are elicited by antisense relA oligomers. These results may explain the in vitro effects of relA antisense oligomers on fibrosarcoma cell growth and adhesion.

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Prostaglandin E2 enhances transforming growth factor-beta 1 and TGF-beta receptors synthesis: An in vivo and in vitro study

Prostaglandins Leukotrienes and Essential Fatty Acids ◽

10.1016/j.plefa.2006.01.003 ◽

2006 ◽

Vol 74 (3) ◽

pp. 183-192 ◽

Cited By ~ 20

Author(s):

G.O. Ramirez-Yañez ◽

S. Hamlet ◽

A. Jonarta ◽

G.J. Seymour ◽

A.L. Symons

Keyword(s):

Growth Factor ◽

Prostaglandin E2 ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

In Vitro Study ◽

Tgf Beta ◽

Beta Receptors ◽

Growth Factor Beta

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Regulation of adhesion and growth of fibrosarcoma cells by NF-kappa B RelA involves transforming growth factor beta

Molecular and Cellular Biology ◽

10.1128/mcb.14.8.5326-5332.1994 ◽

1994 ◽

Vol 14 (8) ◽

pp. 5326-5332

Author(s):

J R Perez ◽

K A Higgins-Sochaski ◽

J Y Maltese ◽

R Narayanan

Keyword(s):

Cell Adhesion ◽

Growth Factor ◽

Transforming Growth Factor Beta ◽

Antisense Oligonucleotides ◽

Transforming Growth Factor ◽

Tgf Beta ◽

Nf Kappa B ◽

Growth Factor Beta ◽

In Vitro Effects

The NF-kappa B transcription factor is a pleiotropic activator that participates in the induction of a wide variety of cellular genes. Antisense oligomer inhibition of the RelA subunit of NF-kappa B results in a block of cellular adhesion and inhibition of tumor cell growth. Investigation of the molecular basis for these effects showed that in vitro inhibition of the growth of transformed fibroblasts by relA antisense oligonucleotides can be reversed by the parental-cell-conditioned medium. Cytokine profile analysis of these cells treated with relA antisense oligonucleotides revealed inhibition of transforming growth factor beta 1 (TGF-beta 1 to the transformed fibroblasts reversed the inhibitory effects of relA antisense oligomers on soft agar colony formation and cell adhesion to the substratum. Direct inhibition of TGF-beta 1 expression by antisense phosphorothioates to TGF-beta 1 mimicked the in vitro effects of blocking cell adhesion that are elicited by antisense relA oligomers. These results may explain the in vitro effects of relA antisense oligomers on fibrosarcoma cell growth and adhesion.

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Transforming growth factor beta suppresses human immunodeficiency virus expression and replication in infected cells of the monocyte/macrophage lineage.

Journal of Experimental Medicine ◽

10.1084/jem.173.3.589 ◽

1991 ◽

Vol 173 (3) ◽

pp. 589-597 ◽

Cited By ~ 109

Author(s):

G Poli ◽

A L Kinter ◽

J S Justement ◽

P Bressler ◽

J H Kehrl ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

T Cell ◽

Growth Factor ◽

Cell Line ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Tgf Beta ◽

Immunodeficiency Virus ◽

Growth Factor Beta

The pleiotropic immunoregulatory cytokine transforming growth factor beta (TGF-beta) potently suppresses production of the human immunodeficiency virus (HIV), the causative agent of the acquired immunodeficiency syndrome, in the chronically infected promonocytic cell line U1. TGF-beta significantly (50-90%) inhibited HIV reverse transcriptase production and synthesis of viral proteins in U1 cells stimulated with phorbol myristate acetate (PMA) or interleukin 6 (IL-6). Furthermore, TGF-beta suppressed PMA induction of HIV transcription in U1 cells. In contrast, TGF-beta did not significantly affect the expression of HIV induced by tumor necrosis factor alpha (TNF-alpha). These suppressive effects were not mediated via the induction of interferon alpha (IFN-alpha). TGF-beta also suppressed HIV replication in primary monocyte-derived macrophages infected in vitro, both in the absence of exogenous cytokines and in IL-6-stimulated cultures. In contrast, no significant effects of TGF-beta were observed in either a chronically infected T cell line (ACH-2) or in primary T cell blasts infected in vitro. Therefore, TGF-beta may play a potentially important role as a negative regulator of HIV expression in infected monocytes or tissue macrophages in infected individuals.

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Transforming growth factor beta 1 (TGF-beta 1) induced neutrophil recruitment to synovial tissues: implications for TGF-beta-driven synovial inflammation and hyperplasia.

Journal of Experimental Medicine ◽

10.1084/jem.173.5.1121 ◽

1991 ◽

Vol 173 (5) ◽

pp. 1121-1132 ◽

Cited By ~ 129

Author(s):

R A Fava ◽

N J Olsen ◽

A E Postlethwaite ◽

K N Broadley ◽

J M Davidson ◽

...

Keyword(s):

Growth Factor ◽

Synovial Tissue ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Biologically Active ◽

Tgf Beta ◽

Histological Techniques ◽

Growth Factor Beta

We have studied the consequences of introducing human recombinant transforming growth factor beta 1 (hrTGF-beta 1) into synovial tissue of the rat, to begin to better understand the significance of the fact that biologically active TGF-beta is found in human arthritic synovial effusions. Within 4-6 h after the intra-articular injection of 1 microgram of hrTGF-beta 1 into rat knee joints, extensive recruitment of polymorphonuclear leukocytes (PMNs) was observed. Cytochemistry and high resolution histological techniques were used to quantitate the influx of PMNs, which peaked 6 h post-injection. In a Boyden chamber assay, hrTGF-beta 1 at 1-10 fg/ml elicited a chemotactic response from PMNs greater in magnitude than that evoked by FMLP, establishing that TGF-beta 1 is an effective chemotactic agent for PMNs in vitro as well as in vivo. That PMNs may represent an important source of TGF-beta in inflammatory infiltrates was strongly suggested by a demonstration that stored TGF-beta 1 was secreted during phorbol myristate acetate-stimulated degranulation in vitro. Acid/ethanol extracts of human PMNs assayed by ELISA contained an average of 355 ng of TGF/beta 1 per 10(9) cells potentially available for secretion during degranulation of PMNs. [3H]Thymidine incorporation in vivo and autoradiography of tissue sections revealed that widespread cell proliferation was triggered by TGF-beta 1 injection. Synovial lining cells and cells located deep within the subsynovial connective tissue were identified as sources of at least some of the new cells that contribute to TGF-beta 1-induced hyperplasia. Our results demonstrate that TGF-beta is capable of exerting pathogenic effects on synovial tissue and that PMNs may represent a significant source of the TGF-beta present in synovial effusions.

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Captopril reverses high-glucose-induced growth effects on LLC-PK1 cells partly by decreasing transforming growth factor-beta receptor protein expressions.

Journal of the American Society of Nephrology ◽

10.1681/asn.v781207 ◽

1996 ◽

Vol 7 (8) ◽

pp. 1207-1215 ◽

Cited By ~ 1

Author(s):

J Y Guh ◽

M L Yang ◽

Y L Yang ◽

C C Chang ◽

L Y Chuang

Keyword(s):

Growth Factor ◽

Transforming Growth Factor Beta ◽

High Glucose ◽

Transforming Growth Factor ◽

Receptor Protein ◽

Tgf Beta ◽

Beta Receptor ◽

Protein Expressions ◽

Beta Receptors ◽

Growth Factor Beta

Transforming growth factor beta (TGF-beta) may be important in the pathogenesis of diabetic nephropathy, and captopril is effective in treating this disorder. However, the mechanisms of this therapeutic effect as related to TGF-beta and its receptors are not known. Thus, the effects of captopril on cellular growth, TGF-beta 1, and TGF-beta receptors were studied in LLC-PK1 cells cultured in normal (11 mM) or high glucose (27.5 mM). This study found that glucose dose-dependently inhibited cellular mitogenesis while inducing hypertrophy in these cells at 72 h of culture, concomitantly with enhanced TGF-beta 1 messenger RNA (mRNA) and TGF-beta receptor Types I and II protein expressions. Captopril dose-dependently (0.1 to 10 mM) increased cellular mitogenesis and inhibited hypertrophy in these cells. Moreover, captopril also decreased TGF-beta receptor Types I and II protein expressions dose-dependently. However, TGF-beta 1 mRNA was not affected by captopril. It was concluded that high glucose decreased cellular mitogenesis while increasing hypertrophy concomitantly with increased TGF-beta 1 mRNA and TGF-beta receptors in LLC-PK1 cells. Captopril can reverse high-glucose-induced growth effects by decreasing TGF-beta receptor protein expressions.

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Expression and secretion of transforming growth factor-beta by bleomycin-stimulated rat alveolar macrophages

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1993.264.1.l36 ◽

1993 ◽

Vol 264 (1) ◽

pp. L36-L42 ◽

Cited By ~ 2

Author(s):

E. M. Denholm ◽

S. M. Rollins

Keyword(s):

Growth Factor ◽

Alveolar Macrophages ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Chemotactic Activity ◽

Beta Activity ◽

Dependent Manner ◽

Tgf Beta ◽

Growth Factor Beta

Bleomycin-induced fibrosis in rodents has been used extensively as a model of human pulmonary fibrosis. The influx of monocytes observed during the early stages of fibrosis is at least partially regulated by the elaboration of chemotactic factors in the lung. Exposure of alveolar macrophages (AM phi) to bleomycin either in vivo or in vitro stimulated secretion of monocyte chemotactic activity (MCA). This MCA has been previously characterized as being primarily due to fibronectin fragments. The present experiments revealed that bleomycin also induced AM phi to secrete a second chemotactic factor, transforming growth factor-beta (TGF-beta). However, the TGF-beta secreted by macrophages was in latent form, since no TGF-beta activity was detected unless AM phi conditioned medium (CM) was acid-activated. After acidification, chemotactic activity in CM from AM phi stimulated with bleomycin in vitro was increased by 3.6, whereas activity in AM phi CM from fibrotic rats increased by 2 and that of a bleomycin-stimulated AM phi cell line increased by 1.6. This acid-activatable chemotactic activity was inhibited by antibody to TGF-beta. Bleomycin-stimulated AM phi s secreted significantly more TGF-beta than did unstimulated controls. Further, in vitro exposure of AM phi to bleomycin induced TGF-beta mRNA expression in a time- and concentration-dependent manner, with maximal mRNA being detected following a 16-h incubation with 1 microgram/ml bleomycin.

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Transcriptional modulation of transin gene expression by epidermal growth factor and transforming growth factor beta

Molecular and Cellular Biology ◽

10.1128/mcb.8.6.2479-2483.1988 ◽

1988 ◽

Vol 8 (6) ◽

pp. 2479-2483

Author(s):

C M Machida ◽

L L Muldoon ◽

K D Rodland ◽

B E Magun

Keyword(s):

Gene Expression ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Prolonged Treatment ◽

Transcriptional Level ◽

Tgf Beta ◽

Epidermal Growth ◽

Growth Factor Beta

Transin is a transformation-associated gene which is expressed constitutively in rat fibroblasts transformed by a variety of oncogenes and in malignant mouse skin carcinomas but not benign papillomas or normal skin. It has been demonstrated that, in nontransformed Rat-1 cells, transin RNA expression is modulated positively by epidermal growth factor (EGF) and negatively by transforming growth factor beta (TGF-beta); other peptide growth factors were found to have no effect on transin expression. Results presented here indicate that both protein synthesis and continuous occupancy of the EGF receptor by EGF were required for sustained induction of transin RNA. Treatment with TGF-beta inhibited the ability of EGF to induce transin, whether assayed at the transcriptional level by nuclear run-on analysis or at the level of transin RNA accumulation by Northern (RNA) blot analysis of cellular RNA. TGF-beta both blocked initial induction of transin transcription by EGF and halted established production of transin transcripts during prolonged treatment. These results suggest that TGF-beta acts at the transcriptional level to antagonize EGF-mediated induction of transin gene expression.

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The types II and III transforming growth factor-beta receptors form homo-oligomers.

The Journal of Cell Biology ◽

10.1083/jcb.126.1.139 ◽

1994 ◽

Vol 126 (1) ◽

pp. 139-154 ◽

Cited By ~ 131

Author(s):

Y I Henis ◽

A Moustakas ◽

H Y Lin ◽

H F Lodish

Keyword(s):

Growth Factor ◽

Cell Surface ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Type Ii ◽

Tgf Beta ◽

Double Labeling ◽

Beta Receptors ◽

Growth Factor Beta ◽

In Cells

Affinity-labeling experiments have detected hetero-oligomers of the types I, II, and III transforming growth factor beta (TGF-beta) receptors which mediate intracellular signaling by TGF-beta, but the oligomeric state of the individual receptor types remains unknown. Here we use two types of experiments to show that a major portion of the receptor types II and III forms homo-oligomers both in the absence and presence of TGF-beta. Both experiments used COS-7 cells co-transfected with combinations of these receptors carrying different epitope tags at their extracellular termini. In immunoprecipitation experiments, radiolabeled TGF-beta was bound and cross-linked to cells co-expressing two differently tagged type II receptors. Sequential immunoprecipitations using anti-epitope monoclonal antibodies showed that type II TGF-beta receptors form homo-oligomers. In cells co-expressing epitope-tagged types II and III receptors, a low level of co-precipitation of the ligand-labeled receptors was observed, indicating that some hetero-oligomers of the types II and III receptors exist in the presence of ligand. Antibody-mediated cross-linking studies based on double-labeling immunofluorescence explored co-patching of the receptors at the cell surface on live cells. In cells co-expressing two differently tagged type II receptors or two differently tagged type III receptors, forcing one receptor into micropatches by IgG induced co-patching of the receptor carrying the other tag, labeled by noncross-linking monovalent Fab'. These studies showed that homo-oligomers of the types II and III receptors exist on the cell surface in the absence or presence of TGF-beta 1 or -beta 2. In cells co-expressing types II and III receptors, the amount of heterocomplexes at the cell surface was too low to be detected in the immunofluorescence co-patching experiments, confirming that hetero-oligomers of the types II and III receptors are minor and probably transient species.

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