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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of mRNA for transforming growth factor alpha (TGF-alpha) and TGF-beta 1 during the fetal development of mice was evaluated by in situ hybridization. TGF-alpha mRNA was detected in 9- and 10-day fetuses but was absent in older fetuses. TGF-alpha mRNA-containing cells were found in the placenta, otic vesicle, oral cavity, pharyngeal pouch, first and second branchial arches, and developing kidneys. mRNA for TGF-beta 1 was present in hematopoietic cells of blood islands and capillaries and in the liver as it began to bud off on day 10 and function as a hematopoietic organ.
Mol Cell Biol 1988 Aug
PMID:Developmental expression of transforming growth factors alpha and beta in mouse fetus. 321 Nov 46

Transforming growth factors (TGF) are defined as biologically active polypeptides which reversibly confer the transformed phenotype onto untransformed cultured cells. They have been subdivided into two classes: type alpha and type beta TGFs. TGF-beta acts synergistically with TGF-alpha in inducing phenotypic transformation. TGF-beta can also act as a negative autocrine growth factor. A human 1050-bp EcoRi cDNA fragment was used to map the human locus for TGF-beta by Southern blotting of DNA prepared from 17 human X Chinese hamster somatic cell hybrids. The human-specific restriction fragments segregated with human chromosome 19 in all of 14 informative hybrids. All other human chromosomes were discordant with the TGF-beta bands in at least four hybrids. After in situ hybridization of the tritiated TGF-beta probe to normal human metaphase spreads, 151 silver grains were scored in 54 cells. Of 24 grains over chromosome 19, 16 grains (11%) lay over region 19q13.1----q13.3. Of the 54 cells analyzed, 16 (30%) had label over region 19q13.1----q13.3. Thus, TGFB is assigned to chromosome 19, subbands q13.1----q13.3. The Tgf-beta locus in the mouse was mapped to chromosome 7 by hybridizing a murine cDNA probe to a Chinese hamster X mouse hybrid panel. Human chromosome 19 and proximal mouse chromosome 7 share another four homologous loci.
Somat Cell Mol Genet 1986 May
PMID:Transforming growth factor beta gene maps to human chromosome 19 long arm and to mouse chromosome 7. 345 57

dGMP, dAMP, dCMP and dTMP were incubated with cis PDD in a nucleotide/Pt ratio 1:1 for 72 h. Following hydrolysis, Pt derivatives of the bases were separated on Sephadex G10 columns. dGMP, dAMP and dCMP reacted with cis PDD but only dGMP reacted completely. All the nucleotides mentioned above formed adducts with cis PDD with a metal to ligand ratio 1:1. Moreover an ML2 complex was isolated after the reaction of dGMP with cis PDD. These Pt-base(s) complexes were eluted from the columns in separate peaks. UV spectra of the complexes differed from the standard ones. In some peaks, eluted separately from the standards, no Pt was detected. The samples eluted in these peaks had UV spectra different from the standards. They may represent products of base degradation.
Mol Biol Rep 1983 Aug
PMID:Separation of platinated derivatives of nucleic acid bases on Sephadex G10. 668 25

A synthetic DNA construct has been developed as a standard molecule whereby murine cytokine mRNA molecules can be quantified by the reverse transcription-polymerase chain reaction (RT-PCR). The construct, designated Cytoquant 1, allows the quantification of murine IL-1 alpha, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IFN-gamma, TNF-alpha, TGF-beta, GM-CSF, CD4, CD8, HPRT and beta-actin mRNA levels. This technique is based on the amplification of a transcribed RNA molecule from Cytoquant 1 as an internal standard control in both the RT and PCR reactions. The quantification data from these analyses are expressed in absolute values, i.e. molecules/cell, which allows the data derived from separate experiments to be compared. In this study, mRNAs encoding beta-actin, IL-10, IFN-gamma and GM-CSF have been quantitated in both Th1 and Th2 cell clones with, and without, stimulation. The quantitative analysis data are highly reproducible and cytokine mRNA concentrations are reflective of restricted cytokine secretion patterns. Furthermore, constitutive cytokine mRNA levels are detectable in resting cells, eliminating the need for exogenous stimulation. The high degree of sensitivity and accuracy make this methodology uniquely suited for the study of T-cell subset cytokine expression in both in vivo and in vitro biological models.
Mol Immunol 1995 Sep
PMID:A synthetic standard DNA construct for use in quantification of murine cytokine mRNA molecules. 747 5

The proliferation of sparse cultures of RIE-1 rat intestinal epithelial cells was potently inhibited by transforming growth factor type beta 1 (TGF-beta 1), with a half-maximal effect at 10-30 pg/ml. As judged by [3H]thymidine incorporation assays, this growth inhibitory action became apparent 4-6 h after addition of TGF-beta 1 to the cells. RIE-1 cells express high-affinity (KD approximately 5.6 pM) receptors for 125I-TGF-beta 1. Affinity cross linking experiments labelled two major species of putative TGF-beta 1 receptors with M(r) values of 235,000 and 65,000. Medium conditioned by confluent cultures of RIE-1 cells contained latent TGF-beta-like activity that was activated at low pH. These findings support a model of autocrine growth inhibition of intestinal crypt cells by TGF-beta.
Biochem Mol Biol Int 1995 May
PMID:Evidence for autocrine growth inhibition of rat intestinal epithelial (RIE-1) cells by transforming growth factor type-beta. 749 69

Using as a model system, primary cultures of porcine Leydig cells, we have shown that transforming growth factor-beta 1 (TGF-beta 1) (2 ng/ml, 72 h) antagonizes the stimulatory action of insulin-like growth factor-I (IGF-I) on luteinizing hormone (LH/hCG) receptors. We therefore investigated the action of TGF-beta 1 on the different components of the IGF system, namely, IGF-I, II, IGF binding proteins (IGFBPs) and IGF-I receptor present in testicular Leydig cells. TGF-beta 1 was shown to decrease in a dose and time dependent manner the binding of 125I-IGF-I to Leydig cells. The maximal (40% decrease) effect was obtained with 1.3 ng/ml (0.05 nM) after 72 h of treatment. Such a decrease in IGF-I binding by TGF-beta 1 treatment was shown to be related to the number of receptor but not to their affinity. Affinity labeling of these receptors by covalently binding them to 125I-IGF-I with disuccinimidyl suberate and subsequent electrophoretic analysis of the labeled complex revealed that the inhibitory action of TGF-beta 1 (2 ng/ml, 72 h) occurs at the level of a 135 kDa protein which represents the classical form of the binding subunit of the IGF-I receptor. Moreover, our study indicates that TGF-beta 1 was unable to affect the other components of the IGF system in cultured porcine Leydig cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1994 Mar
PMID:Effect of transforming growth factor-beta 1 on the insulin-like growth factor system in cultured porcine Leydig cells. 751 40

Hepatocyte growth factor (HGF) and its receptor, the product of c-MET proto-oncogene, are highly expressed in both fetal and adult lung, though their physiologic functions in the lung are largely unknown. In the present study, we examined whether alveolar type II cells in the lung are the target of HGF and whether HGF has any effects on growth of these cells. The alveolar epithelial type II cells were isolated from the lungs of adult male Sprague-Dawley rats by elastase digestion, and the cells were used to determine whether they express HGF and c-MET mRNAs and whether recombinant HGF has any effect on their DNA synthesis in primary culture. The effects were further compared with those induced by epidermal growth factor (EGF), acidic fibroblast growth factor (aFGF), transforming growth factor-alpha (TGF-alpha), and transforming growth factor-beta 1 (TGF-beta 1). Northern blot analysis and in situ hybridization revealed that type II cells express c-MET mRNA but not HGF mRNA. HGF stimulated [3H]thymidine incorporation into type II cells in primary cultures. An increase was also seen in labeling index as determined by nuclear immunostaining of bromodeoxyuridine-incorporated DNA. While aFGF (200 ng/ml) exerted an effect comparable to HGF (25 ng/ml) on DNA synthesis in type II cells, EGF (20 ng/ml) and TGF-alpha (100 ng/ml) had lesser effects. TGF-beta 1, a potent inhibitor of epithelial cell proliferation, at 0.25 to 2 ng/ml, did not inhibit HGF-induced [3H]thymidine incorporation into type II cells. The results indicate that HGF exerts its effects on type II cells as a potent mitogen by a paracrine mode of action.
Am J Respir Cell Mol Biol 1995 Feb
PMID:Hepatocyte growth factor stimulates DNA synthesis in alveolar epithelial type II cells in vitro. 753 19

Fibroblasts are the central target cell in pulmonary fibrotic diseases, and their proliferation is mediated largely by platelet-derived growth factor (PDGF) isoforms secreted by activated lung macrophages. Several other macrophage-derived cytokines that are increased during fibrogenesis, including interleukin-1 beta and transforming growth factor-beta 1 (TGF-beta 1), could potentially modulate the mitogenic and chemotactic activity of PDGF by altering the expression of cell-surface PDGF receptors on fibroblasts. The PDGF receptor system on fibroblasts from a variety of tissues shows heterogeneous responses to TGF-beta 1. Lung fibroblasts have not been investigated in this regard. TGF-beta 1 downregulated the gene expression of the 6.5 kb PDGF-alpha receptor (PDGF-R alpha) transcript in normal human lung fibroblasts in a concentration-dependent fashion that was maximal at 3 ng/ml TGF-beta 1; this corresponded with a decrease in cell-surface PDGF-R alpha as measured by radioligand binding assays using [125I]PDGF-AA. The TGF-beta 1-induced down-regulation of the PDGF-R alpha gene was rapid (maximal suppression by 2 h post-treatment) and preceded the decrease in cell-surface alpha-receptor (maximal reduction by 6 h post-treatment). TGF-beta 1 treatment did not alter the rate of PDGF-R alpha mRNA degradation following the inhibition of transcription using actinomycin D, indicating that TGF-beta 1 increases PDGF-R alpha transcription. Scatchard analysis of saturation binding data showed that TGF-beta 1 decreased the number of [125I]PDGF-AA binding sites 5-fold without affecting receptor affinity. [125I]PDGF-AB binding sites were downregulated approximately 25%, and the number of [125I]PDGF-BB binding sites was not changed by TGF-beta 1 treatment, indicating that the PDGF-beta receptor was not affected. TGF-beta 1 reduced the mitogenic and chemotactic response to PDGF-AA by > 90%, whereas these biologic response to PDGF-AB and PDGF-BB were inhibited 50% to 80%. The proliferative and chemotactic responses of fibroblasts during tissue remodeling or during lung fibrosis are likely controlled by a complex network involving PDGF isoforms and cytokines that modify the PDGF receptor system.
Am J Respir Cell Mol Biol 1995 Oct
PMID:Transforming growth factor beta 1 downregulates the platelet-derived growth factor alpha-receptor subtype on human lung fibroblasts in vitro. 754 80

MRF4, MyoD, myogenin, and Myf-5 are muscle-specific basic helix-loop-helix transcription factors that share the ability to activate the expression of skeletal muscle genes such as those encoding alpha-actin, myosin heavy chain, and the acetylcholine receptor subunits. The muscle regulatory factors (MRFs) also exhibit the unique capacity to initiate the myogenic program when ectopically expressed in a variety of nonmuscle cell types, most notably C3H10T1/2 fibroblasts (10T1/2 cells). The commitment of myoblasts to terminal differentiation, although positively regulated by the MRFs, also is controlled negatively by a variety of agents, including several growth factors and oncoproteins such as fibroblast growth factor (FGF-2), transforming growth factor beta 1 (TGF-beta 1), and Ras p21Val. The molecular mechanisms by which these varied agents alter myogenic terminal differentiation events remain unclear. In an effort to establish whether Ras p21Val represses MRF activity by directly targeting the MRF proteins, we examined the DNA binding and transcription activation potentials of MRF4 and MyoD when expressed in 10T1/2 cells or in 10T1/2 cells expressing Ras p21Val. Our results demonstrate that Ras p21Val inhibits terminal differentiation events by targeting the basic domain of the MRFs, and yet the mechanism underlying this inhibition does not involve altering the DNA binding or the inherent transcriptional activity of these regulatory factors. In contrast, FGF-2 and TGF-beta 1 block terminal differentiation by repressing the transcriptional activity of the MRFs. We conclude that the Ras p21Val block in differentiation operates via an intracellular signaling pathway that is distinct from the FGF-2 and TGF-beta 1 pathways.
Mol Cell Biol 1995 Oct
PMID:Ras p21Val inhibits myogenesis without altering the DNA binding or transcriptional activities of the myogenic basic helix-loop-helix factors. 756 69

We used monoclonal antibodies to study expression and extracellular matrix (ECM) incorporation of tenascin (Tn) and isoforms of fibronectin (Fn) in BEAS 2B immortalized human bronchial epithelial cells and the regulation of their synthesis by transforming growth factor (TGF)-beta 1 and -beta 2. In immunofluorescence microscopy, the control cells appeared negative for Tn. Extradomain A (EDA)-Fn was mainly seen in association with ECM fibers and, in a few cells, in an intracellular location. Immunoreactivity for oncofetal (onc)-Fn and extradomain B (EDB)-Fn was only seen in a few cells. In TGF-beta 1- and -beta 2-treated cells, a greatly enhanced immunostaining for Tn and three isoforms of Fn was seen both as to the number of positive cells and to the amount of immunoreactive material around them. In Western blotting of the untreated cells, EDA-Fn and onc-Fn were detected in the cell-free ECM and in the culture medium, whereas EDB-Fn was not detectable. An enhanced secretion and deposition of both EDA-Fn and onc-Fn and also secretion of EDB-Fn was seen upon treatment with TGF-beta s. In TGF-beta-treated cells, Tn was found exclusively in the ECM and not in the culture medium as shown by Western blotting of cell-free ECM and culture medium, respectively. Accentuation of tenascin staining in TGF-beta-treated cells was due to a greatly enhanced production of M(r) 280,000 and M(r) 190,000 isoforms of Tn.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1995 Nov
PMID:Transforming growth factor-beta regulates the expression of fibronectin and tenascin in BEAS 2B human bronchial epithelial cells. 757 94


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