scholarly journals Differential effects of transforming growth factor-beta on the synthesis of extracellular matrix proteins by normal fetal rat calvarial bone cell populations.

1988 ◽  
Vol 106 (3) ◽  
pp. 915-924 ◽  
Author(s):  
J L Wrana ◽  
M Maeno ◽  
B Hawrylyshyn ◽  
K L Yao ◽  
C Domenicucci ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Plasminogen Activator Inhibitor ◽  
Bone Cell ◽  
Cell Populations ◽  
Tgf Beta ◽  
Differential Effects ◽  
Fetal Rat ◽  
Activator Inhibitor ◽  
Stimulation Of

To determine the effects of transforming growth factor-beta (TGF-beta) on the different cell types that exist in bone, cell populations (I-IV), progressively enriched in osteoblastic cells relative to fibroblastic cells, were prepared from fetal rat calvaria using timed collagenase digestions. TGF-beta did not induce anchorage-independent growth of these cells, nor was anchorage-dependent growth stimulated in most populations studied, despite a two- to threefold increase in the synthesis of cellular proteins. In all populations the synthesis of secreted proteins increased 2-3.5-fold. In particular, collagen, fibronectin, and plasminogen activator inhibitor synthesis was stimulated. However, different degrees of stimulation of individual proteins were observed both within and between cell populations. A marked preferential stimulation of plasminogen activator inhibitor was observed in each population, together with a slight preferential stimulation of collagen; the effect on collagen expression being directed primarily at type I collagen. In contrast, the synthesis of SPARC (secreted protein acidic rich in cysteine/osteonectin was stimulated approximately two-fold by TGF-beta, but only in fibroblastic populations. Collectively, these results demonstrate that TGF-beta stimulates matrix production by bone cells and, through differential effects on individual matrix components, may also influence the nature of the matrix formed by different bone cell populations. In the presence of TGF-beta, osteoblastic cells lost their polygonal morphology and alkaline phosphatase activity was decreased, reflecting a suppression of osteoblastic features. The differential effects of TGF-beta on bone cell populations are likely to be important in bone remodeling and fracture repair.

scholarly journals Platelets stimulate endothelial cells to synthesize type 1 plasminogen activator inhibitor. Evaluation of the role of transforming growth factor beta

Blood ◽  
1991 ◽  
Vol 77 (5) ◽  
pp. 1013-1019 ◽  
Author(s):  
SR Slivka ◽  
DJ Loskutoff
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Plasminogen Activator Inhibitor ◽  
Tgf Beta ◽  
Growth Factor Beta ◽  
Activator Inhibitor ◽  
Pai 1

Abstract A model system consisting of thrombin-stimulated bovine platelet releasates (PRthr) and bovine aortic endothelial cells (BAEs) was developed to determine if the interaction between platelets and endothelial cells regulates fibrinolysis. Zymographic analysis indicated that PRthr treatment of BAEs decreases urokinase and increases type 1 plasminogen activator inhibitor (PAI-1) activity. Although PRthr did not affect the overall rate of BAE protein synthesis, it increased PAI-1 biosynthesis within 6 hours. This increase was complete by 12 hours, with maximum stimulation at 10 to 15 micrograms/mL PRthr (1 microgram approximately 10(7) platelets). Neutralizing antibodies to transforming growth factor beta (TGF beta) reduced this effect by 75%. Treatments that activate latent TGF beta (eg, acidification or plasmin) increased this effect approximately fivefold, suggesting that TGF beta in PRthr exists in both a latent (approximately 80%) and an active (approximately 20%) form. In contrast to PRthr, adenosine diphosphate-prepared platelet releasates did not increase PAI-1 synthesis before acidification, indicating that they contain only the latent form of TGF beta. These results suggest that platelets can modulate the fibrinolytic system of the endothelium through the release of TGF beta, and that the mechanism by which the platelets are activated can influence the relative amount of active TGF beta.

scholarly journals Platelets stimulate endothelial cells to synthesize type 1 plasminogen activator inhibitor. Evaluation of the role of transforming growth factor beta

Blood ◽  
1991 ◽  
Vol 77 (5) ◽  
pp. 1013-1019 ◽  
Author(s):  
SR Slivka ◽  
DJ Loskutoff
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Plasminogen Activator Inhibitor ◽  
Tgf Beta ◽  
Growth Factor Beta ◽  
Activator Inhibitor ◽  
Pai 1

A model system consisting of thrombin-stimulated bovine platelet releasates (PRthr) and bovine aortic endothelial cells (BAEs) was developed to determine if the interaction between platelets and endothelial cells regulates fibrinolysis. Zymographic analysis indicated that PRthr treatment of BAEs decreases urokinase and increases type 1 plasminogen activator inhibitor (PAI-1) activity. Although PRthr did not affect the overall rate of BAE protein synthesis, it increased PAI-1 biosynthesis within 6 hours. This increase was complete by 12 hours, with maximum stimulation at 10 to 15 micrograms/mL PRthr (1 microgram approximately 10(7) platelets). Neutralizing antibodies to transforming growth factor beta (TGF beta) reduced this effect by 75%. Treatments that activate latent TGF beta (eg, acidification or plasmin) increased this effect approximately fivefold, suggesting that TGF beta in PRthr exists in both a latent (approximately 80%) and an active (approximately 20%) form. In contrast to PRthr, adenosine diphosphate-prepared platelet releasates did not increase PAI-1 synthesis before acidification, indicating that they contain only the latent form of TGF beta. These results suggest that platelets can modulate the fibrinolytic system of the endothelium through the release of TGF beta, and that the mechanism by which the platelets are activated can influence the relative amount of active TGF beta.

scholarly journals Control of junB and extracellular matrix protein expression by transforming growth factor-beta 1 is independent of simian virus 40 T antigen-sensitive growth-sensitive growth-inhibitory events.

1991 ◽  
Vol 11 (2) ◽  
pp. 972-978 ◽  
Author(s):  
M Laiho ◽  
L Rönnstrand ◽  
J Heino ◽  
J A Decaprio ◽  
J W Ludlow ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Extracellular Matrix ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Simian Virus 40 ◽  
Plasminogen Activator Inhibitor ◽  
Simian Virus ◽  
T Antigen ◽  
Tgf Beta ◽  
Plasminogen Activator Inhibitor 1

Treatment of Mv1Lu mink lung epithelial cells with transforming growth factor-beta 1 (TGF-beta 1) prevents phosphorylation of the retinoblastoma susceptibility gene product, RB, in late G1 phase of the cell cycle, which is thought to retain RB in a growth-suppressive state. This effect is paralleled by cell cycle arrest in late G1 (M. Laiho, J. A. DeCapric, J. W. Ludlow, D. M. Livingston, and J. Massagué, Cell 62:175-185, 1990). Arrest can be prevented by expression of simian virus 40 T antigen, which binds to underphosphorylated RB, presumably blocking its growth-suppressive activity. The response of cells to TGF-beta 1, however, is complex and includes changes in the levels of expression of genes encoding nuclear transcription factors and extracellular matrix components. To define the relationships among various components of the TGF-beta 1 response, we have investigated the effect of TGF-beta 1 on cells whose growth-inhibitory response to this factor is prevented by T antigen. TGF-beta 1 addition to exponentially growing Mv1Lu cells increased the levels of junB mRNA and of three extracellular matrix proteins: plasminogen activator inhibitor-1, fibronectin, and thrombospondin. Kinetically, the effects on junB and plasminogen activator inhibitor-1 expression occurred faster (half-maximal at 1 to 2 h) than the effects on fibronectin and thrombospondin expression (half-maximal at 6 to 10 h). These effects either preceded or overlapped, respectively, the withdrawal of Mv1Lu cells from the cell cycle. Expression of a transfected T-antigen gene in Mv1Lu cells, however, did not prevent any of these responses to TGF-beta 1. The results indcate that TGF-B1-stimulated expression of junB and extracellular matrix proteins in Mv1Lu cells can occur independently of the T-antigen-sensitive events that lead to growth arrest.

scholarly journals Serum factors, growth factors and UDP-sugar metabolism in bovine articular cartilage chondrocytes

1994 ◽  
Vol 303 (3) ◽  
pp. 713-721 ◽  
Author(s):  
G E Ysart ◽  
R M Mason
Keyword(s):  
Growth Factors ◽  
Articular Cartilage ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Sugar Metabolism ◽  
Tgf Beta ◽  
Serum Factors ◽  
Bovine Articular Cartilage ◽  
Stimulation Of

1. The effect of different batches of fetal bovine serum and of growth factors on [35S]sulphate incorporation into glycosaminoglycans and on UDP-sugar pools in explant cultures of bovine articular cartilage was investigated. 2. [35S]Sulphate incorporation was variably stimulated between 1.2- and 3.5-fold by four different batches of serum. The UDP-glucuronate pool size expanded 4.3-6.5-fold in the presence of serum, even in those cultures in which little stimulation of [35S]sulphate incorporation occurred. The UDP-N-acetylhexosamine and UDP-hexose pools expanded by about 1.5- and 2.0-fold respectively in the presence of serum. UDP-xylose was not detected. 3. Equilibrium-labelling and pulse-chase experiments with D-[1-3H]glucose indicated that the rate of flux through the UDP-sugar pools was unaffected by serum. UDP-hexose, UDP-N-acetylhexosamine and UDP-glucuronate have approximate half-lives (t1/2) of 7, 12 and 3-4 min respectively. At equilibrium, the 3H specific activities of UDP-hexose and UDP-N-acetylhexosamine were very similar but that for the UDP-glucuronate pool was much higher, especially in serum-supplemented cultures. The results suggest that UDP-glucuronate synthesis occurs via a pathway which is independent of the main UDP-hexose pathway. 4. Supplementing cultures with heat-treated serum had no effect on the serum-induced expansion of UDP-sugar pools but stimulation of [35S]sulphate incorporation into glycosaminoglycans was 50% lower than for native serum. Acid-treated serum promoted a 2-fold expansion of the UDP-glucuronate and UDP-N-acetylhexosamine pool over that obtained with native serum but was 20% less effective in stimulating [35S]sulphate incorporation than the latter. Prior dialysis of serum had no effect on its modulatory action on either [35S]sulphate incorporation or on the size of UDP-sugar pools. 5. Insulin-like growth factor 1 (IGF-1), transforming growth factor beta-1 (TGF beta-1), platelet-derived growth factor (PDGF) (BB homodimer) and epidermal growth factor (EGF) all stimulated [35S]sulphate incorporation into glycosaminoglycans as expected. The UDP-glucuronate pool expanded by 1.5- and 2.0-fold in the presence of IGF-1 and TGF beta-1 respectively, and by about 1.8-fold in the presence of PDGF or EGF. None of the factors investigated, or combinations of IGF-1 and TGF beta-1 or IGF-1 and EGF, stimulated expansion of the UDP-glucuronate pool to the same extent as native serum.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Transforming growth factors-beta 1 and beta 2 are mitogens for rat Schwann cells.

1989 ◽  
Vol 109 (6) ◽  
pp. 3419-3424 ◽  
Author(s):  
A J Ridley ◽  
J B Davis ◽  
P Stroobant ◽  
H Land
Keyword(s):  
Growth Factor ◽  
Schwann Cell ◽  
Dna Synthesis ◽  
Schwann Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Tgf Beta ◽  
Beta 2 ◽  
Cell Mitogen ◽  
Stimulation Of

Transforming growth factor-beta 1 (TGF-beta 1) and TGF-beta 2 were found to be potent mitogens for purified rat Schwann cells, each stimulating DNA synthesis in quiescent cells and also increasing their proliferation rate. Half-maximal stimulation of DNA synthesis occurred at approximately 0.1 ng/ml TGF-beta 1 or TGF-beta 2. Mitogenic stimulation by TGF-beta 1 and TGF-beta 2 was enhanced by forskolin, which activates adenylate cyclase, at concentrations up to 0.5 microM forskolin. However, at 5 microM forskolin, the synergistic interaction between forskolin and TGF-beta 1 was abolished. These results are in contrast to the observed synergy between forskolin and another Schwann cell mitogen, glial growth factor (GGF). Both 0.5 and 5 microM forskolin were found to enhance the stimulation of DNA synthesis by partially purified GGF (GGF-CM). As well as being functionally distinct, TGF-beta 1 and GGF-CM activities were also physically separable by chromatography on a Superose 12 gel permeation column. Thus, TGF-beta 1 and beta 2 are rat Schwann cell mitogens, and Schwann cells are one of the few normal cell populations to respond mitogenically to TGF-beta.

Sign in / Sign up

Export Citation Format

Share Document