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

In the present study, we have characterized the cell surface receptors for transforming growth factor-beta (TGF-beta) on monolayer cultures of stromal cells prepared from human endometrial biopsies, and on a human endometrial epithelial cell line (RL95-2) using affinity cross-link labeling techniques. On the stromal cells, five TGF-beta binding proteins were identified. Analysis of the sensitivity of these proteins to dithiothreitol and phosphatidylinositol-specific phospholipase C, together with results from immunoprecipitations with antibodies against the type II and III TGF-beta receptors, confirmed that three of these binding proteins correspond to the cloned type I, II, and III TGF-beta receptors. The other two binding proteins observed exhibit the characteristics of isoform-specific GPI-anchored TGF-beta binding proteins. On RL95-2 cells, three TGF-beta binding proteins, corresponding to the type I, II, and III TGF-beta receptors, were identified. The receptors which we have characterized on endometrial cells are responsive to physiological concentrations of TGF-beta as demonstrated by the effect of TGF-beta on endometrial cell proliferation. Accordingly, these receptors have the potential to respond to the TGF-beta isoforms which have recently been detected in the endometrium in an autocrine and/or paracrine manner.
Mol Cell Endocrinol 1995 Apr 28
PMID:Transforming growth factor-beta receptors on human endometrial cells: identification of the type I, II, and III receptors and glycosyl-phosphatidylinositol anchored TGF-beta binding proteins. 764 53

Intercellular signaling molecules of the transforming growth factor-beta (TGF-beta) superfamily are required for pattern formation in many multicellular organisms. The decapentaplegic (dpp) gene of Drosophila melanogaster has several developmental roles. To improve our understanding of the evolutionary diversification of this large family we identified dpp in the grasshopper Schistocerca americana. S. americana diverged from D. melanogaster approximately 350 million years ago, utilizes a distinct developmental program, and has a 60-fold-larger genome than D. melanogaster. Our analyses indicate a single dpp locus in D. melanogaster and S. americana, suggesting that dpp copy number does not correlate with increasing genome size. Another TGF-beta superfamily member, the D. melanogaster gene 60A, is also present in only one copy in each species. Comparison of homologous sequences from D. melanogaster, S. americana, and H. sapiens, representing roughly 900 million years of evolutionary distance, reveals significant constraint on sequence divergence for both dpp and 60A. In the signaling portion of the dpp protein, the amino acid identity between these species exceeds 74%. Our results for the TGF-beta superfamily are consistent with current hypotheses describing gene duplication and diversification as a frequent response to high levels of selective pressure on individual family members.
J Mol Evol 1995 Aug
PMID:Identification of two Drosophila TGF-beta family members in the grasshopper Schistocerca americana. 766 45

3T3-L1 preadipocytes differentiate into cells having the biochemical properties of adipocytes; tumor necrosis factor-alpha (TNF), retinoic acid (RA), and transforming growth factor-beta (TGF-beta), attenuate this process. Inhibition of differentiation by these agents, thought to be at the level of transcription, has been investigated by examining the accumulation of mRNA for six transcription factors and the autocrine growth factor interleukin 6 (IL-6). Upon induction of differentiation, a rapid and major accumulation of c-fos and jun-B mRNA was observed that returned to near basal levels within 4-6 h. In contrast, c-jun mRNA, although rapidly expressed following induction of differentiation, remained at relatively constant levels throughout the time course. Exposure of the cells to 5 nM TNF potentiated the accumulation of all 3 mRNAs but most significantly c-jun (12-fold), which remained elevated for at least 24 h after treatment. In control differentiating cells, krox-20 and fox-B were expressed transiently, 30 min to 2 h, while fra-1 mRNA accumulated over an extended period, 1 to 8 h. Again, TNF enhanced the accumulation of these mRNAs. Accumulation of mRNA for C/EBP, a transcription factor proposed to control expression of genes involved in the terminally differentiated state was attenuated after exposure of the cells to TNF. C/EBP expression was also inhibited in cells exposed to RA or TGF-beta. IL-6 mRNA was expressed briefly (30 min to 2 h) and again transiently (at 8 h after induction of differentiation). TNF treatment markedly enhanced accumulation of IL-6 message.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem
PMID:Regulation of transcription factor mRNA accumulation during 3T3-L1 preadipocyte differentiation by antagonists of adipogenesis. 769 71

Deposition of amyloid fibrils in the brain is a histopathologic hallmark of Alzheimer disease (AD) and beta-amyloid protein (A beta), the principal component of amyloid fibrils, has been implicated in the neuropathogenesis of AD. In the present study, we first developed an in vitro model of A beta-induced neurodegeneration using human fetal brain-cell cultures and then tested the hypothesis that cytokines modulate A beta-induced neurodegeneration. When brain-cell cultures were exposed to A beta, marked neuronal loss (60% of neurons by microscopic assessment) and functional impairment (i.e., reduction in uptake of [3H]gamma-aminobutyric acid) were observed after 6 d of incubation. A beta-induced neurodegeneration was dose-dependent with maximal effect at 100 microM. Although interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-alpha had a nominal effect, both the beta 1 and beta 2 isoforms of transforming growth factor-beta dose-dependently protected > 50% of neurons against A beta-induced injury. IL-4 also proved to be neuro-protective. A beta-induced neurodegeneration was accompanied by microglial cell proliferation and enhanced release of IL-1, IL-6, and TNF-alpha. These findings are consistent with the emerging concept that AD is an inflammatory disease and may lead to new therapeutic strategies aimed at reducing A beta-induced neurotoxicity.
Mol Chem Neuropathol
PMID:Transforming growth factor-beta protects human neurons against beta-amyloid-induced injury. 770 6

Accumulation of oxidized low density lipoproteins in macrophages and smooth muscle cells causes foam cell formation, an initial step in atherosclerosis. Active oxygen species are considered important in the pathogenesis of the disease. Antioxidants, such as tocopherols and tocotrienols have been considered to prevent the deleterious effects of active oxygen species. We found native low density lipoproteins can stimulate directly smooth muscle cell proliferation, it is associated with an increase of protein kinase C activity. d-alpha-Tocopherol, biologically most active form of vitamin E, inhibits both cell proliferation and protein kinase C activity. The effect of d-alpha-tocopherol is not related to its radical scavenging properties. Transforming growth factor-beta secreted by smooth muscle cells as growth inhibitor. Low density lipoproteins decrease the release of transforming growth factor-beta from smooth muscle cells thus activating growth. d-alpha-Tocopherol activates the cellular release of transforming growth factor-beta. These new aspects explain the important role of low density lipoproteins and vitamin E in increasing and decreasing the risk of atherosclerosis, respectively.
Biochem Mol Biol Int 1995 Jan
PMID:New roles of low density lipoproteins and vitamin E in the pathogenesis of atherosclerosis. 773 26

Growth/differentiation factor-9 (GDF-9) is a previously described member of the transforming growth factor-beta superfamily expressed specifically in the ovary in adult mice. Using in situ hybridization methods, we have localized the expression of GDF-9 messenger RNA (mRNA) exclusively to oocytes. GDF-9 mRNA was detected in oocytes at all stages of follicular development, except in primordial follicles, in both neonatal and adult ovaries. GDF-9 mRNA continued to be expressed in oocytes after ovulation, but disappeared by 1.5 days after fertilization. Based on Western analysis of ovarian extracts using antibodies raised against recombinant GDF-9 protein, GDF-9 mRNA expressed by oocytes appears to be translated. A human homolog of GDF-9 was isolated from a complementary DNA library prepared from adult ovary mRNA. The predicted human protein is 90% identical to murine GDF-9 in the mature portion of the molecule. These results are significant because no other growth factor-like molecules have been shown to be expressed specifically by oocytes and, together with results of previous studies, suggest that ovarian development and function are regulated by factors produced by both oocytes and support cells of the ovary.
Mol Endocrinol 1995 Jan
PMID:Oocyte-specific expression of growth/differentiation factor-9. 776 Aug 46

Although transforming growth factor-beta s (TGF-beta s) are expressed widely in both adult and embryonic rat heart, both mRNA and protein expression increase following ischemic injury. Furthermore, exogenous administration of TGF-beta decreases cardiac damage following ischemia-reperfusion in rats. We have found that treatment of primary cultures of neonatal rat cardiomyocytes or cardiac fibroblasts with TGF-beta 1, 2, or 3 results in increased expression of TGF-beta 1, 2, and 3 mRNA. TGF-beta 2 was generally the least effective isoform in inducing TGF-beta expression. In cardiac fibroblasts mRNA expression of all TGF-beta s increased 2-3-fold following 1 h of treatment and decreased to control levels by 8 h which was accompanied by a 2.5- and 2.3-fold increase in TGF-beta 1 and 2 protein secretion, respectively. By 48 h of treatment mRNA levels for TGF-beta s 2 and 3 were less than 10% of control levels. In cardiomyocytes two-five-fold increases in mRNA levels were observed following 1-24 h of TGF-beta 1 treatment, but TGF-beta 1 and 3 mRNA levels returned to control values by 48 h while TGF-beta 2 mRNA expression remained elevated. TGF-beta 1 and 2 protein secreted by the cardiac myocytes was increased 2.9- and 1.7-fold, respectively. Autoinduction of TGF-beta s may play a beneficial role in cardiac wound healing by sustaining transient increases in TGF-beta levels from either endogenous synthesis or exogenous application.
J Mol Cell Cardiol 1995 Feb
PMID:Autoinduction of mRNA and protein expression for transforming growth factor-beta S in cultured cardiac cells. 777 87

We investigated the contribution of c-fos protooncogene in the mitogenic effect of transforming growth factor-beta (TGF beta) in serum-deprived, confluent rat calvaria osteoblastic cells. The TGF beta-induced growth in these cells was associated with an immediate and transient c-fos mRNA accumulation, similar to the inductive effect of fetal calf serum. To assess the role of c-fos in the response to TGF beta, we used a c-fos antisense (AS) oligonucleotide displaying duplex formation with rat c-fos mRNA. Studies of AS and sense (S) uptake by osteoblastic cells demonstrated that incorporation of labeled oligomers was maximal at 2 h, and the incorporated AS oligonucleotide remained intact for 24 h. Immunofluorescence analysis of c-Fos-labeled cells demonstrated that AS, but not S, oligonucleotide reduced c-Fos protein expression, suggesting specific efficient inhibition of c-fos translation by the AS oligomer. Proliferation assays showed that cell growth induced by fetal calf serum was inhibited by the AS, but not by the S oligonucleotide, in both normal rat osteoblasts and ROS 17/2.8 osteosarcoma cells, demonstrating efficient and specific blockage of cell growth by the AS oligomer. The mitogenic effect of TGF-beta was abolished in cells cultured in the presence of AS, whereas S had no effect, showing that c-fos is required for TGF beta-induced osteoblast cell growth. The results show that the induction of c-fos is implicated in the mitogenic effect of TGF beta in osteoblastic cells and provide a cellular mechanism involved in the response of these cells to TGF beta.
Mol Endocrinol 1995 Feb
PMID:c-fos protooncogene is involved in the mitogenic effect of transforming growth factor-beta in osteoblastic cells. 777 69

The effect of beta-alanyl-L-histidinato zinc (AHZ) on protein components in osteoblastic MC3T3-E1 cells was investigated. Cells were cultured for 3 days at 37 degrees C in CO2 incubator in plastic dishes containing alpha-modified minimum essential medium supplemented with 10% fetal bovine serum. After the cultures, the medium was exchanged for that containing 0.1% bovine serum albumin plus various concentrations of AHZ or other reagents, and the cells were cultured further 3 or 6 days. The homgenate of cells was analyzed with SDS-polyacrylamide gel electrophoresis (SDS-PAGE). The presence of AHZ (10(-7) to 10(-5) M) caused an appreciable increase of many protein components in cells. Especially, the 67 killo-dalton (kDa) and 44 kDa proteins which are the major components from control cells were clearly increased by the presence of AHZ. Furthermore, the concentrations of osteocalcin, insulin-like growth factor-I and transforming growth factor-beta in the culture medium secreted from osteoblastic cells were markedly increased by the presence of AHZ (10(-6) and 10(-5) M). The effect of AHZ was a greater than that of zinc sulfate (10(-6) and 10(-5) M). The present findings suggest that AHZ can increase many proteins which are involved in the stimulation of bone formation and cell proliferation in osteoblastic cells.
Mol Cell Biochem 1994 Jul 27
PMID:Effect of beta-alanyl-L-histidinato zinc on protein components in osteoblastic MC3T3-El cells: increase in osteocalcin, insulin-like growth factor-I and transforming growth factor-beta. 784 70

To assess the temporal and spatial expression of the matrix-associated proteoglycan, biglycan, in a model of chronic hyperoxia-induced lung injury, changes in mRNA and protein were examined using Northern blot analyses and immunohistochemistry. Newborn rats were exposed to 85% or 100% oxygen for 6 and 4 wk, respectively. Exposure to 85% oxygen for up to 6 wk resulted in a reduction in lung surface area and the development of focal areas of fibrosis. In contrast, exposure to 100% oxygen resulted in gross alterations in lung histology with greatly enlarged airspaces and septal thickening. Biglycan mRNA increased at 3 to 5 wk in control animals, then returned to baseline, while oxygen-exposed animals showed a further increase after 2 to 4 wk of exposure. Immunoreactive biglycan decreased with postnatal age but increased in alveolar cells of animals exposed to 100% oxygen for 4 wk and in alveolar cells and along alveolar septae of animals exposed to 85% oxygen for 6 wk. We speculate that biglycan binds growth factors such as transforming growth factor-beta near these cells, acting in an autoregulatory fashion to support epithelial cell proliferation and inhibit mesenchymal cell proliferation.
Am J Respir Cell Mol Biol 1994 Nov
PMID:Temporal and spatial expression of biglycan in chronic oxygen-induced lung injury. 794 80


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