Transforming growth factor-β is a potent inhibitor of basal and stimulated relaxin release by porcine luteal cells maintained in monolayer culture

1992 ◽  
Vol 135 (3) ◽  
pp. 543-550 ◽  
Author(s):  
M. J. Taylor ◽  
C. L. Clark
Keyword(s):  
Growth Factor ◽  
Time Course ◽  
Transforming Growth Factor ◽  
Protein A ◽  
Plaque Assay ◽  
Transforming Growth Factor Β ◽  
Luteal Cell ◽  
Prostaglandin E ◽  
Hormone Release ◽  
Luteal Cells

ABSTRACT The effect of transforming growth factor-β (TGF-β) on relaxin release by porcine large luteal cells (LLC) was examined by use of a reverse haemolytic plaque assay. In this assay, mixed luteal cells were co-cultured in monolayers with protein A-coupled sheep erythrocytes. In the presence of complement and porcine relaxin antiserum, a zone of haemolysis (a plaque) developed around relaxin-releasing LLCs. The rate of plaque development in time-course experiments and the average size of plaque areas were used to monitor the rate of relaxin release and cumulative amounts of hormone respectively. Monolayers were bathed in medium containing TGF-β alone, or in the co-presence of a stimulatory secretagogue (prostaglandin E2; PGE2). Exposure of luteal cell-containing monolayers to TGF-β (1 ng/1–100 μg/l) elicited a dose-related inhibition in the rate of basal relaxin release. Minimal and maximal concentrations were approximately 10 ng/l and 10 μg/l respectively. Treatment with 1 μg TGF-β/l reduced the cumulative amount of relaxin released to 63 ± 6% of control values (mean ± s.d., P < 0·05, n = 6; averaged over the whole course of the experimental incubation). Exposure of monolayers treated with TGF-β to the relaxin-stimulatory secretagogue PGE2 (0·1 μmol) resulted in a significant (P < 0·05) increase in the amount of relaxin released by TGF-β-suppressed LLCs, and restored rates of hormone release to control levels. This is evidence that TGF-β and PGE2 interact antagonistically in the modulation of relaxin. The effect of TGF-β was strictly time-dependent. A period of at least 16 h of treatment with TGF-β was required to induce an inhibitory effect on relaxin. These results implicate TGF-β as a novel inhibitor of relaxin release, and the presence of TGF-β in porcine luteal tissue suggests that such regulation may be achieved via paracrine or autocrine routes. It is possible that TGF-β interacts functionally during luteal life with other secretagogues to achieve integrated control of hormone release. Journal of Endocrinology (1992) 135, 543–550

Effects of transforming growth factor-β on normal clonal bone cell populations

1991 ◽  
Vol 69 (2-3) ◽  
pp. 132-140 ◽  
Author(s):  
Rebecca Ber ◽  
Takao Kubota ◽  
Jaro Sodek ◽  
Jane E. Aubin
Keyword(s):  
Alkaline Phosphatase ◽  
Growth Factor ◽  
Phosphatase Activity ◽  
Alkaline Phosphatase Activity ◽  
Transforming Growth Factor ◽  
Bone Cells ◽  
Transforming Growth Factor Β ◽  
Prostaglandin E ◽  
Intracellular Camp ◽  
Type I

Although transforming growth factor-β (TGF-β) has been implicated in the local regulation of bone growth and remodelling, its specific effects on different subpopulations of bone cells have not been elucidated. Cells derived from bone are known to be heterogeneous and include both cells of different lineages and osteoblastic populations with different levels of expression of osteoblast-associated properties. Consequently, we have isolated clonal populations of bone cells to examine more precisely the effects of TGF-β on individual subpopulations. Several clonal populations were isolated by limiting dilution from cells derived from 21-day-old fetal rat calvaria. Two of these clones, RCA 11 and RCB 2, were used here. While the two clones responded similarly to parathyroid hormone (PTH) and isoproterenol (ISP) with increases in intracellular cAMP, prostaglandin E2 (PGE2) elicited a 10-fold higher response in RCB 2 cells compared with RCA 11. RCB 2 cells expressed a 10-fold higher alkaline phosphatase activity compared with RCA 11. Both clones synthesized a variety of bone matrix associated proteins, but only RCA 11 synthesized SPP-1 (osteopontin) constitutively. TGF-β stimulated growth of RCB 2 cells after 24 and 48 h of treatment, but had no effect on growth of RCA 11. TGF-β supported anchorage-independent growth of RCB 2 cells, but not that of RCA 11. A 24-h exposure to TGF-β decreased cAMP responsiveness to PTH and ISP slightly in both clones, but had no effect on PGE2 responses. Significant reductions in alkaline phosphatase activity were seen in both clones after 24- and 48-h treatments with TGF-β. Total protein synthesis as measured by [35S]methionine incorporation was stimulated significantly in both clones, but TGF-β selectively stimulated type I collagen compared with type III collagen. SPARC (osteonectin) and secreted phosphoprotein 1 (SPP-1; osteopontin) were stimulated by TGF-β in both RCA 11 and RCB 2 cells. These results indicate that individual clonal populations of cells within bone may be modulated differentially by TGF-β.Key words: transforming growth factor-β, osteoblasts, clonal cell lines, matrix synthesis.

Transforming growth factor-β inhibits surfactant protein A expression in vitro

1992 ◽  
Vol 1123 (3) ◽  
pp. 257-262 ◽  
Author(s):  
Jeffrey A. Whitsett ◽  
Ailsa Budden ◽  
William M. Hull ◽  
Jean C. Clark ◽  
Michael A. O'Reilly
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Protein A ◽  
Transforming Growth Factor Β ◽  
Surfactant Protein ◽  
Surfactant Protein A

An In Silico Investigation of Potential EGFR Inhibitors for the Clinical Treatment of Colorectal Cancer

2019 ◽  
Vol 18 (27) ◽  
pp. 2355-2366 ◽  
Author(s):  
Manisha Majhi ◽  
Meer Asif Ali ◽  
Akanksha Limaye ◽  
Kritika Sinha ◽  
Praveena Bairagi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Docking ◽  
Growth Factor ◽  
Virtual Screening ◽  
Transforming Growth Factor ◽  
Transmembrane Protein ◽  
Protein A ◽  
Growth Factor Receptor ◽  
Transforming Growth Factor Β ◽  
Egfr Inhibitors

Colorectal cancer possesses the third highest diagnostic rate and is the second leading cause of cancer death in the USA as reported by NIH. Epidermal Growth Factor Receptor (EGFR), a transmembrane protein, participates in PLC gamma-1, RAS-RAF-MEK-MAPKs, phosphatidylinositol-3 kinase, Akt pathways and plays a key role in normal functioning of cell division, cell differentiation, apoptosis and migration. This protein is found to be overexpressed in more than 60% of the colorectal cancers. Overexpressed EGFR advances the tumorigenic properties through cell cycle dysregulation and activates signaling pathways linked to cancer such as WNT/β-catenin, transforming growth factor β (TGF-β) and phosphoinositide-3-kinase (PI3K). Inhibiting the overexpressed EGFR protein has been proposed for the treatment and many inhibitors have been reported suppressing the activity of EGFR. However, patients in malignant state of cancer show resistance to those inhibitors, which open a wide space to research for the discovery of novel inhibitors. The present study employed Molecular Docking and Virtual Screening to find novel inhibitors with high affinity against EGFR. Molecular docking of existing inhibitors resulted in the compound titled as BGB-283 (PubChem CID-89670174) having the highest score, which was subjected to similarity search to retrieve the drugs with similar structure. The virtual screening concluded a compound SCHEMBL18435602 (PubChem CID-126517400) which revealed a better affinity with the target protein. A comparative study of both the compounds showed equivalent pharmacokinetic properties. These identified drugs have a high potential to act as EGFR inhibitors and can show promising results in the research of colorectal cancer.

scholarly journals Role of transforming growth factor-β1in down-regulating TNF production by alveolar macrophages during asbestos-induced pulmonary fibrosis

1996 ◽  
Vol 5 (1) ◽  
pp. 37-42 ◽  
Author(s):  
Irma Lemaire ◽  
Sophie Ouellet
Keyword(s):  
Growth Factor ◽  
Alveolar Macrophages ◽  
Transforming Growth Factor ◽  
Neutralizing Antibody ◽  
Transforming Growth Factor Β ◽  
Significant Inhibition ◽  
Prostaglandin E ◽  
Tumour Necrosis Factor Production

Activation of alveolar macrophages (AM) for tumour necrosis factor production is suppressed initially during the inflammatory response to fibrogenic dusts. We investigated the mechanisms involved in TNF suppression, notably the role of other AM-derived mediators including prostaglandin E2(PGE2), transforming growth factor-β1(TGF-β1), and interleukin 6 (IL-6). The action of PGE2and TGF-β1, on AM was different. At physiologically relevant doses (25–300 pg/ml), PGE2did not cause significant inhibition of Hpopolysaccharide (Lps)-induced TNF release by AMin vitrobut stimulated IL-6 (up to six fold), an inhibitor of AM-derived TNT. In contrast, TGF-β1(0.5–50 ng/ml) inhibited both LPS-induced TNT and IL-6 release by 50% but had no effect on PGE2production by AM. To determine the respective contribution of these different inhibitors in TNF suppression, AM from rats exposed to fibrogenic asbestos for weeks were treated with neutralizing antibody against TGF-β1or indomethacin, an inhibitor of PGE2synthesis. Treatment of rat AM with anti-TGF-β1but not indomethacin, abrogated the observed TNT suppression. These results suggest that an autocrine, TGF-β1-dependent mechanism is involved in the down-regulation of TNF production by rat AM from animals with lung fibrosis.

scholarly journals Relative Potencies of 1,25-(OH)2D3and 19-Nor-1,25-(OH)2D2on Inducing Differentiation and Markers of Bone Formation in MG-63 Cells

2001 ◽  
Vol 12 (7) ◽  
pp. 1468-1474
Author(s):  
JANE L. FINCH ◽  
ADRIANA S. DUSSO ◽  
TRICIA PAVLOPOULOS ◽  
EDUARDO A. SLATOPOLSKY
Keyword(s):  
Vitamin D ◽  
Growth Factor ◽  
Bone Formation ◽  
Cell Line ◽  
Vitamin D Receptor ◽  
Time Course ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Nuclear Antigen ◽  
Alp Activity

Abstract. 19-Nor-1,25-(OH)2D2, an analog of 1,25-(OH)2D3, is used to treat secondary hyperparathyroidism because it suppresses parathyroid hormone synthesis and secretion with lower calcemic and phosphatemic activities. 19-Nor-1,25-(OH)2D2is approximately 10 times less active than 1,25-(OH)2D3in promoting bone resorption, which accounts in part for the low potency of this analog in increasing serum calcium and phosphorus. Concern that 19-nor-1,25-(OH)2D2also could be less potent than 1,25-(OH)2D3on bone formation led to a comparison of the potency of both compounds on osteoblasts. In the human osteoblast-like cell line MG-63, 1,25-(OH)2D3and 19-nor-1,25-(OH)2D2had a similar potency in upregulating vitamin D receptor content and suppressing proliferation. Both sterols caused a similar reduction in DNA content and proliferating cell nuclear antigen protein expression. Time-course and dose-response studies on 1,25-(OH)2D3and 19-nor-1,25-(OH)2D2induction of the marker of bone formation, osteocalcin, showed overlapping curves. The effects on alkaline phosphatase (ALP) activity also were studied in MG-63 cells that had been co-treated with either sterol and transforming growth factor-β, an enhancer of 1,25-(OH)2D3—induced ALP activity in this cell line. Transforming growth factor-β alone had no effect, whereas 1,25-(OH)2D3and 19-nor-1,25-(OH)2D2increased ALP activity similarly. These studies demonstrate that 19-nor-1,25-(OH)2D2has the same potency as 1,25-(OH)2D3not only in inducing vitamin D receptor content, osteocalcin levels, and ALP activity but also in controlling osteoblastic growth. Therefore, it is unlikely that 19-nor-1,25-(OH)2D2would have deleterious effects on bone remodeling.

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