scholarly journals Retinoic acid and transforming growth factor β differentially inhibit platelet-derived-growth-factor-induced Ito-cell activation

1991 ◽  
Vol 278 (1) ◽  
pp. 43-47 ◽  
Author(s):  
B H Davis ◽  
U R Rapp ◽  
N O Davidson
Keyword(s):  
Retinoic Acid ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Cell Activation ◽  
Cellular Proliferation ◽  
Transforming Growth Factor ◽  
Platelet Derived Growth Factor ◽  
Tgf Beta ◽  
Ito Cell ◽  
Ito Cells

Sinusoidal Ito cells (stellate or fat-storing cells) undergo excessive cellular proliferation before the establishment and progression of hepatic fibrosis and cirrhosis. Retinoic acid and transforming growth factor beta (TGF beta) both inhibit Ito-cell [3H]thymidine incorporation in serum-containing media. Serum-induced mitogenicity was dependent on platelet-derived growth factor (PDGF). Additionally, pre-treatment of Ito cells with retinoic acid and TGF beta blocked PDGF-induced cell proliferation. TGF beta, but not retinoic acid, diminished PDGF-receptor and smooth-muscle alpha-actin abundance.

In vitro modulation of endothelial fenestrae: opposing effects of retinoic acid and transforming growth factor beta

1988 ◽  
Vol 91 (2) ◽  
pp. 313-318
Author(s):  
T. Lombardi ◽  
R. Montesano ◽  
M.B. Furie ◽  
S.C. Silverstein ◽  
L. Orci
Keyword(s):  
Endothelial Cells ◽  
Retinoic Acid ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Surface Density ◽  
Transforming Growth Factor ◽  
Control Cell ◽  
Tgf Beta ◽  
Growth Factor Beta

Cultured endothelial cells isolated from fenestrated capillaries express many properties characteristic of their in vivo differentiated phenotype, including the formation of a limited number of fenestrae. In this study, we have investigated whether physiological factors that control cell differentiation might regulate the surface density of fenestrae in capillary endothelial cells. We have found that treatment of the cultures with retinoic acid (10 microM) induces a more than threefold increase in the surface density of endothelial fenestrae, whereas transforming growth factor beta (TGF beta) (2 ng ml-1) causes a sevenfold decrease in the surface density of these structures. These results show that the expression of endothelial fenestrae is susceptible to bidirectional modulation by physiological signals, and suggest that retinoids and TGF beta may participate in the regulation of fenestral density of capillary endothelium in vivo.

scholarly journals Retinoic acid induces transforming growth factor-beta 2 in cultured keratinocytes and mouse epidermis.

1989 ◽  
Vol 1 (1) ◽  
pp. 87-97 ◽  
Author(s):  
A B Glick ◽  
K C Flanders ◽  
D Danielpour ◽  
S H Yuspa ◽  
M B Sporn
Keyword(s):  
Retinoic Acid ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Biologically Active ◽  
Tgf Beta ◽  
Mouse Epidermis ◽  
Cultured Keratinocytes ◽  
Growth Factor Beta ◽  
Beta 2

We have studied the functional interaction between retinoic acid and transforming growth factor-beta (TGF-beta), using the mouse epidermis as a model system. Treatment with retinoic acid increases expression of TGF-beta 2 in cultured keratinocytes in vitro, as well as in the epidermis in vivo. This TGF-beta 2 is secreted in a biologically active form that can bind to surface receptors, in contrast to most other conditions in which TGF-beta is secreted in a latent form. Specific antibodies to TGF-beta 2 partially reverse the ability of retinoic acid to inhibit DNA synthesis in cultured keratinocytes. The regulation of TGF-beta 2 expression by retinoic acid may have important physiological and pharmacological roles in the maintenance of epidermal homeostasis.

scholarly journals Carrageenans inhibit growth-factor binding

1993 ◽  
Vol 289 (2) ◽  
pp. 331-334 ◽  
Author(s):  
R Hoffman
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Platelet Derived Growth Factor ◽  
Transforming Growth Factor Alpha ◽  
Fibroblast Growth ◽  
Tgf Beta ◽  
Factor Alpha ◽  
Growth Factor Beta ◽  
Kappa Carrageenan

Carrageenans, a family of polysulphated carbohydrates, inhibited binding of basic fibroblast growth factor (bFGF), transforming growth factor beta 1 (TGF beta 1) and platelet-derived growth factor (PDGF). iota-Carrageenan was the most potent bFGF antagonist (IC50 = 0.4 +/- 0.1 microgram/ml), kappa-carrageenan was the most potent PDGF antagonist (IC50 = 1.7 +/- 1.3 micrograms/ml) and lambda-carrageenan was the most potent TGF beta 1 antagonist (IC50 = 19 +/- 2 micrograms/ml). None of the carrageenans, at concentrations up to 200 micrograms/ml, inhibited binding of insulin-like growth factor 1 or transforming growth factor alpha. Carrageenans are selective growth-factor antagonists and have potential for the treatment of disorders associated with the over-production of certain growth factors.

scholarly journals A bone marrow stromal cell line is a source and target for platelet- derived growth factor

Blood ◽  
1993 ◽  
Vol 81 (10) ◽  
pp. 2547-2553 ◽  
Author(s):  
SL Abboud
Keyword(s):  
Bone Marrow ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Stromal Cell ◽  
Transforming Growth Factor ◽  
Platelet Derived Growth Factor ◽  
Northern Analysis ◽  
Tgf Beta ◽  
Binding Studies ◽  
A Chain

Abstract Platelet-derived growth factor (PDGF) stimulates multipotent and erythroid progenitors as well as stromal fibroblasts. Any of the three dimeric forms of PDGF (AA, AB, or BB) could potentially interact with these cells; however, the precise cellular origin of PDGF production in the bone marrow microenvironment is not known. In the present study, we found that medium conditioned by MBA-2, murine bone marrow-derived endothelial cells, contains PDGF activity that competes for [125I]PDGF binding to human foreskin fibroblasts and is mitogenic for these fibroblasts. Northern analysis of poly(A)+ RNA from MBA-2 shows the expression of both PDGF A-chain and B-chain mRNAs. Because cytokines such as transforming growth factor-beta (TGF-beta) regulate hematopoiesis and stimulate PDGF in certain mesenchymal cells, we determined whether TGF-beta influences PDGF secretion and gene expression in MBA-2. TGF-beta induced PDGF A-chain and B-chain mRNAs and the release of PDGF activity. Each of the three PDGF isoforms also stimulated DNA synthesis in MBA-2, but with different potency (BB = AB = AA). Ligand binding studies showed specific binding of labeled PDGF BB and, to a lesser extent, PDGF AA isoform, consistent with predominant expression of the PDGF-beta receptor in MBA-2. These data show that murine endothelial stromal cells release PDGF activity and respond to PDGF. Local production of PDGF in the marrow microenvironment may play an important role in regulating hematopoietic and stromal cell proliferation.

Regulation of fibroblast-mediated collagen gel contraction by platelet-derived growth factor, interleukin-1 alpha and transforming growth factor-beta 1

1992 ◽  
Vol 102 (2) ◽  
pp. 315-322 ◽  
Author(s):  
A. Tingstrom ◽  
C.H. Heldin ◽  
K. Rubin
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Interleukin 1 ◽  
Collagen Gel ◽  
Platelet Derived Growth Factor ◽  
Tgf Beta ◽  
Collagen Gels ◽  
Collagen Gel Contraction ◽  
Growth Factor Beta

We have examined the effects of three macrophage-derived cytokines, platelet-derived growth factor (PDGF), transforming growth factor-beta 1 (TGF-beta 1) and interleukin-1 alpha (IL-1 alpha) on the contraction of collagen type I gels populated by human foreskin fibroblasts. Contraction was quantified as loss in gel weight. Both PDGF-AA and PDGF-BB were found to induce a rapid collagen-gel contraction. TGF-beta 1 also stimulated gel contraction but with a delayed onset and at a slower rate than the PDGF-stimulated contraction. Rabbit polyclonal IgGs recognizing PDGF-AA and PDGF-BB, respectively, specifically inhibited the effects of the corresponding PDGF isoforms. However, the stimulatory effect of TGF-beta 1 was not affected by any of the anti-PDGF antibodies. The ability of PDGF to stimulate contraction became less pronounced in collagen gel cultures grown in the absence of growth factors over periods of several days. Under the same conditions, the stimulatory effect of TGF-beta 1 was not reduced. The reduced response to PDGF may be due to reduced tension on fibroblasts growing in collagen gels, since fibroblasts on free-floating gels showed a marked reduction in PDGF-BB-induced PDGF beta-receptor aggregates when compared to fibroblasts on attached collagen gels. IL-1 alpha inhibited initial collagen gel contraction, and at later stages induced a visible degradation of the collagen gels, presumably due to the generation of collagenase activity. The combination of IL-1 alpha and PDGF-BB stimulated initial collagen gel contraction, although less effectively than PDGF-BB alone.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Selective upregulation of platelet-derived growth factor alpha receptors by transforming growth factor beta in scleroderma fibroblasts.

1992 ◽  
Vol 175 (5) ◽  
pp. 1227-1234 ◽  
Author(s):  
A Yamakage ◽  
K Kikuchi ◽  
E A Smith ◽  
E C LeRoy ◽  
M Trojanowska
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Platelet Derived Growth Factor ◽  
Receptor Subunit ◽  
Tgf Beta ◽  
Low Concentrations ◽  
Receptor Number ◽  
Growth Factor Beta ◽  
Adult Skin

Transforming growth factor beta (TGF-beta), a multifunctional cytokine, is an indirect mitogen for human fibroblasts through platelet-derived growth factor (PDGF), particularly the A ligand-alpha receptor arm of that system. TGF-beta effects on PDGF alpha receptor expression were studied in vitro using ligand binding techniques in three human dermal fibroblast strains: newborn foreskin, adult skin, and scleroderma (systemic sclerosis, SSc). Each cell strain responded differently to TGF-beta. In newborn foreskin fibroblasts, PDGF alpha receptor number decreased in a dose-dependent manner after exposure to low concentrations of TGF-beta (0.1-1 ng/ml). Responses of normal skin fibroblasts were varied, and mean net receptor number was unchanged. Increases in PDGF alpha receptor number by TGF-beta occurred consistently with SSc fibroblasts and low concentrations of TGF-beta (0.1-1 ng/ml) were particularly stimulatory. Increased surface expression of alpha receptor subunit by TGF-beta in SSc fibroblasts correlated with increased new PDGF alpha receptor synthesis as demonstrated by radioimmunoprecipitation analysis of metabolically labeled cells and with increased steady-state levels of corresponding mRNAs. In normal adult skin fibroblasts, TGF-beta had no effect on either synthesis or mRNA expression of alpha receptor subunits. Proliferative responses to PDGF-AA after pretreatment with TGF-beta correlated positively with effects of TGF-beta on expression of alpha receptor subunit. Decreased mitogenic responses to PDGF-AA were observed in foreskin fibroblasts, small changes in responses in adult fibroblasts, and significant increases in SSc fibroblasts. Thus, costimulation with PDGF-AA and TGF-beta selectively enhanced proliferation of fibroblasts with the SSc phenotype. Immunohistochemical examination of SSc and control skin biopsies revealed the presence of PDGF-AA in SSc skin. Data obtained by ligand binding, immunoprecipitation, mRNA, and mitogenic techniques are consistent with the hypothesis that activation of the PDGF-AA ligand/alpha receptor pathway is a characteristic of the SSc fibroblast and may contribute to the expansion of fibroblasts in SSc.

scholarly journals A bone marrow stromal cell line is a source and target for platelet- derived growth factor

Blood ◽  
1993 ◽  
Vol 81 (10) ◽  
pp. 2547-2553 ◽  
Author(s):  
SL Abboud
Keyword(s):  
Bone Marrow ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Stromal Cell ◽  
Transforming Growth Factor ◽  
Platelet Derived Growth Factor ◽  
Northern Analysis ◽  
Tgf Beta ◽  
Binding Studies ◽  
A Chain

Platelet-derived growth factor (PDGF) stimulates multipotent and erythroid progenitors as well as stromal fibroblasts. Any of the three dimeric forms of PDGF (AA, AB, or BB) could potentially interact with these cells; however, the precise cellular origin of PDGF production in the bone marrow microenvironment is not known. In the present study, we found that medium conditioned by MBA-2, murine bone marrow-derived endothelial cells, contains PDGF activity that competes for [125I]PDGF binding to human foreskin fibroblasts and is mitogenic for these fibroblasts. Northern analysis of poly(A)+ RNA from MBA-2 shows the expression of both PDGF A-chain and B-chain mRNAs. Because cytokines such as transforming growth factor-beta (TGF-beta) regulate hematopoiesis and stimulate PDGF in certain mesenchymal cells, we determined whether TGF-beta influences PDGF secretion and gene expression in MBA-2. TGF-beta induced PDGF A-chain and B-chain mRNAs and the release of PDGF activity. Each of the three PDGF isoforms also stimulated DNA synthesis in MBA-2, but with different potency (BB = AB = AA). Ligand binding studies showed specific binding of labeled PDGF BB and, to a lesser extent, PDGF AA isoform, consistent with predominant expression of the PDGF-beta receptor in MBA-2. These data show that murine endothelial stromal cells release PDGF activity and respond to PDGF. Local production of PDGF in the marrow microenvironment may play an important role in regulating hematopoietic and stromal cell proliferation.

scholarly journals Retinoic acid suppresses the response to platelet-derived growth factor in human hepatic Ito-cell-like myofibroblasts: a post-receptor mechanism independent of raf/fos/jun/egr activation

1993 ◽  
Vol 294 (3) ◽  
pp. 785-791 ◽  
Author(s):  
B H Davis ◽  
D Coll ◽  
D W A Beno
Keyword(s):  
Retinoic Acid ◽  
Growth Factor ◽  
Human Liver ◽  
Smooth Muscle Actin ◽  
Platelet Derived Growth Factor ◽  
Type I ◽  
Alpha Smooth Muscle Actin ◽  
Ito Cell ◽  
Ito Cells

Activated Ito-cell-like myofibroblasts proliferate in vivo during human liver injury and subsequent fibrogenesis. To examine the associated regulatory mechanisms, human liver myofibroblasts were characterized after culture purification from mixed liver-cell isolates obtained from perfused normal human livers. The cells resembled rat Ito-cell-derived myofibroblasts expressing desmin and alpha-smooth-muscle actin filaments as well as the interstitial collagens type I and III. [3H]Thymidine incorporation was inducible with platelet-derived growth factor (PDGF) and was suppressible with retinoic acid (RAc) in a concentration-dependent fashion. RAc suppression did not alter PDGF alpha- or beta-receptor abundance or activation. In addition, RAc functioned via a pathway distal or independent of cytoplasmic raf activation (i.e. phosphorylation, kinase function and perinuclear translocation) and nuclear fos, jun and egr expression, as these steps were similarly unaffected by RAc treatment. Since normal Ito cells contain abundant amounts of vitamin A which is lost during activation, these data suggest that retinoids could contribute to the maintenance of the quiescent non-proliferative state by suppressing mitogenesis at a post-cytokine receptor step distal from or independent of fos/jun/egr [e.g. via changes in activator protein-1 (AP-1) binding].

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