scholarly journals Synthesis of transforming growth factor-beta 1 by megakaryocytes and its localization to megakaryocyte and platelet alpha-granules

Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 1946-1955 ◽  
Author(s):  
RA Fava ◽  
TT Casey ◽  
J Wilcox ◽  
RW Pelton ◽  
HL Moses ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Messenger Rna ◽  
Transforming Growth Factor ◽  
Immunoperoxidase Technique ◽  
Storage Site ◽  
Tgf Beta ◽  
Growth Factor Beta

We have directly demonstrated that megakaryocytes are a major site of synthesis and storage of transforming growth factor-beta 1 (TGF/beta 1) by combined immunohistochemical, immunocytochemical, and in situ hybridization methods. The presence of TGF/beta 1 messenger RNA (mRNA) in mature megakaryocytes in adult rat spleen and bone marrow (BM) was established by in situ hybridization. Localization of TGF/beta 1 protein to intact alpha-granules of megakaryocytes, its putative storage site, was accomplished in glycol-methacrylate embedded porcine BM with an immunoperoxidase technique and light microscopy. The TGF/beta 1 was sequestered in intracytoplasmic granules in a pattern virtually identical to that of another alpha-granule marker protein, fibrinogen. This observation strongly suggests packaging of TGF/beta 1 into this organelle within megakaryocytes. That TGF/beta 1 mRNA was localized to megakaryocytes suggests that the TGF/beta 1 found in the alpha-granules in platelets originates with megakaryocyte synthesis. The alpha-granule localization of TGF/beta 1, as well as fibrinogen, was also demonstrated in isolated platelets at the ultrastructural level by electronmicroscopy (EM) and postembedding colloidal-gold immunocytochemistry, thus directly demonstrating that alpha-granules are the final storage site for TGF/beta 1 in mature platelets.

scholarly journals Synthesis of transforming growth factor-beta 1 by megakaryocytes and its localization to megakaryocyte and platelet alpha-granules

Blood ◽  
1990 ◽  
Vol 76 (10) ◽  
pp. 1946-1955 ◽  
Author(s):  
RA Fava ◽  
TT Casey ◽  
J Wilcox ◽  
RW Pelton ◽  
HL Moses ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Messenger Rna ◽  
Transforming Growth Factor ◽  
Immunoperoxidase Technique ◽  
Storage Site ◽  
Tgf Beta ◽  
Growth Factor Beta

Abstract We have directly demonstrated that megakaryocytes are a major site of synthesis and storage of transforming growth factor-beta 1 (TGF/beta 1) by combined immunohistochemical, immunocytochemical, and in situ hybridization methods. The presence of TGF/beta 1 messenger RNA (mRNA) in mature megakaryocytes in adult rat spleen and bone marrow (BM) was established by in situ hybridization. Localization of TGF/beta 1 protein to intact alpha-granules of megakaryocytes, its putative storage site, was accomplished in glycol-methacrylate embedded porcine BM with an immunoperoxidase technique and light microscopy. The TGF/beta 1 was sequestered in intracytoplasmic granules in a pattern virtually identical to that of another alpha-granule marker protein, fibrinogen. This observation strongly suggests packaging of TGF/beta 1 into this organelle within megakaryocytes. That TGF/beta 1 mRNA was localized to megakaryocytes suggests that the TGF/beta 1 found in the alpha-granules in platelets originates with megakaryocyte synthesis. The alpha-granule localization of TGF/beta 1, as well as fibrinogen, was also demonstrated in isolated platelets at the ultrastructural level by electronmicroscopy (EM) and postembedding colloidal-gold immunocytochemistry, thus directly demonstrating that alpha-granules are the final storage site for TGF/beta 1 in mature platelets.

scholarly journals Eosinophils from patients with blood eosinophilia express transforming growth factor beta 1

Blood ◽  
1991 ◽  
Vol 78 (10) ◽  
pp. 2702-2707 ◽  
Author(s):  
DT Wong ◽  
A Elovic ◽  
K Matossian ◽  
N Nagura ◽  
J McBride ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
In Situ Hybridization ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Hypereosinophilic Syndrome ◽  
Tgf Beta ◽  
Blood Eosinophilia ◽  
Growth Factor Beta

Abstract The infiltration of eosinophils into tissues during pathologic responses is often associated with extracellular matrix alterations such as fibrosis. Transforming growth factor-beta 1 (TGF-beta 1) is a well-characterized multifunctional cytokine known to exert potent effects on the extracellular matrix. In this report, we showed the production of TGF-beta 1 by human eosinophils from patients with blood eosinophilia. Northern blot analysis using RNA isolated from eosinophils purified from a patient with the idiopathic hypereosinophilic syndrome (HES) detected the 2.5-kb TGF-beta 1 transcript. In situ hybridization and immunohistochemistry of leukocytes from two patients with HES and two patients with blood eosinophilia localized TGF-beta 1 messenger RNA (mRNA) and protein to eosinophils. No other cell type contained TGF-beta 1 mRNA by in situ hybridization, whereas other leukocytes contained detectable TGF-beta 1 protein by immunohistochemistry. Eosinophils from four normal donors contained little or no detectable TGF-beta 1 protein by immunohistochemistry, whereas eosinophils from two of these four normal donors labeled weakly for TGF-beta 1 mRNA by in situ hybridization. These results show that eosinophils in the peripheral blood of patients with blood eosinophilia can express TGF-beta 1, but that eosinophils in the blood of normal donors contained little or no TGF-beta 1.

scholarly journals Eosinophils from patients with blood eosinophilia express transforming growth factor beta 1

Blood ◽  
1991 ◽  
Vol 78 (10) ◽  
pp. 2702-2707 ◽  
Author(s):  
DT Wong ◽  
A Elovic ◽  
K Matossian ◽  
N Nagura ◽  
J McBride ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
In Situ Hybridization ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Hypereosinophilic Syndrome ◽  
Tgf Beta ◽  
Blood Eosinophilia ◽  
Growth Factor Beta

The infiltration of eosinophils into tissues during pathologic responses is often associated with extracellular matrix alterations such as fibrosis. Transforming growth factor-beta 1 (TGF-beta 1) is a well-characterized multifunctional cytokine known to exert potent effects on the extracellular matrix. In this report, we showed the production of TGF-beta 1 by human eosinophils from patients with blood eosinophilia. Northern blot analysis using RNA isolated from eosinophils purified from a patient with the idiopathic hypereosinophilic syndrome (HES) detected the 2.5-kb TGF-beta 1 transcript. In situ hybridization and immunohistochemistry of leukocytes from two patients with HES and two patients with blood eosinophilia localized TGF-beta 1 messenger RNA (mRNA) and protein to eosinophils. No other cell type contained TGF-beta 1 mRNA by in situ hybridization, whereas other leukocytes contained detectable TGF-beta 1 protein by immunohistochemistry. Eosinophils from four normal donors contained little or no detectable TGF-beta 1 protein by immunohistochemistry, whereas eosinophils from two of these four normal donors labeled weakly for TGF-beta 1 mRNA by in situ hybridization. These results show that eosinophils in the peripheral blood of patients with blood eosinophilia can express TGF-beta 1, but that eosinophils in the blood of normal donors contained little or no TGF-beta 1.

Expression of transforming growth factor beta 2 RNA during murine embryogenesis

Development ◽  
1989 ◽  
Vol 106 (4) ◽  
pp. 759-767 ◽  
Author(s):  
R.W. Pelton ◽  
S. Nomura ◽  
H.L. Moses ◽  
B.L. Hogan
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Post Partum ◽  
Mouse Embryos ◽  
Tgf Beta ◽  
Growth Factor Beta ◽  
Beta 2 ◽  
Temporal And Spatial

We have studied the temporal and spatial expression of transforming growth factor beta 2 (TGF beta 2) RNA in mouse embryos from 10.5 days post coitum (p.c.) to 3 days post partum (p.p.) by in situ hybridization analysis. TGF beta 2 RNA is expressed in a variety of tissues including bone, cartilage, tendon, gut, blood vessels, skin and fetal placenta, and is in general found in the mesenchymal component of these tissues. The expression of TGF beta 2 RNA changes during development in a manner consistent with a role for the gene product in mediating mesenchymal-epithelial interactions.

scholarly journals Epithelium-dependent extracellular matrix synthesis in transforming growth factor-beta 1-growth-inhibited mouse mammary gland.

1990 ◽  
Vol 110 (6) ◽  
pp. 2209-2219 ◽  
Author(s):  
G B Silberstein ◽  
P Strickland ◽  
S Coleman ◽  
C W Daniel
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Messenger Rna ◽  
Transforming Growth Factor ◽  
Type I ◽  
Tgf Beta ◽  
Matrix Synthesis ◽  
The Matrix ◽  
Growth Factor Beta

Exogenous transforming growth factor beta (TGF-beta 1) was shown in earlier studies to reversibly inhibit mouse mammary ductal growth. Using small plastic implants to treat regions of developing mammary glands in situ, we now report that TGF-beta 1 growth inhibition is associated with an ectopic accumulation of type I collagen messenger RNA and protein, as well as the glycosaminoglycan, chondroitin sulfate. Both macromolecules are normal components of the ductal extracellular matrix, which, under the influence of exogenous TGF-beta 1, became unusually concentrated immediately adjacent to the epithelial cells at the tip of the ductal growth points, the end buds. Stimulation of extracellular matrix was confined to aggregations of connective tissue cells around affected end buds and was not present around the TGF-beta 1 implants themselves, indicating that the matrix effect was epithelium dependent. Ectopic matrix synthesis was specific for TGF-beta 1 insofar as it was absent at ducts treated with other growth inhibitors, or at ducts undergoing normal involution in response to endogenous regulatory processes. These findings are consistent with the matrix-stimulating properties of TGF-beta 1 reported for other systems, but differ in their strict dependence upon epithelium. A possible role for endogenous TGF-beta 1 in modulating a mammary epithelium-stroma interaction is suggested.

scholarly journals A second messenger RNA species of transforming growth factor beta 1 in infarcted rat heart.

1991 ◽  
Vol 2 (3) ◽  
pp. 241-249 ◽  
Author(s):  
S W Qian ◽  
P Kondaiah ◽  
W Casscells ◽  
A B Roberts ◽  
M B Sporn
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Rat Heart ◽  
Messenger Rna ◽  
Transforming Growth Factor ◽  
Tissue Injury ◽  
Heart Tissue ◽  
Experimental Myocardial Infarction ◽  
Tgf Beta ◽  
Growth Factor Beta

Transforming growth factor-beta 1 (TGF-beta 1) is encoded predominantly by a 2.4-kb mRNA in most tissues. However, an additional transcript of 1.9 kb can be detected in rat heart after experimental myocardial infarction caused by ligation of the left coronary artery. This transcript level is significantly higher in infarcted heart tissue than in normal heart tissue, suggesting an important role for this mRNA species in response to injury. Structural characterization of the 1.9-kb mRNA showed that it included the entire coding sequence present in the 2.4-kb TGF-beta 1 mRNA, but also contained an additional nonhomologous 3'-untranslated region (UTR). The junction between the shared and unique 3' sequence in the 1.9-kb mRNA occurred only two nucleotides before the proposed polyadenylation site of the rat TGF-beta 1 2.4-kb mRNA. The unique 3'-UTR and the deduced shortened 5'-UTR in the novel 1.9-kb TGF-beta 1 mRNA suggest different transcriptional and translational regulatory mechanisms under conditions of tissue injury.

scholarly journals Transforming growth factor beta downregulates interleukin-1 (IL-1)- induced IL-6 production by human monocytes

Blood ◽  
1990 ◽  
Vol 76 (12) ◽  
pp. 2466-2469
Author(s):  
T Musso ◽  
I Espinoza-Delgado ◽  
K Pulkki ◽  
GL Gusella ◽  
DL Longo ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Messenger Rna ◽  
Transforming Growth Factor ◽  
Interleukin 1 ◽  
Dependent Manner ◽  
Human Monocytes ◽  
Tgf Beta ◽  
Growth Factor Beta ◽  
Dose Dependent

We investigated the effects of transforming growth factor beta (TGF beta) on the induction by interleukin-1 beta (IL-1 beta) of IL-6 in human monocytes. We found that IL-1 beta induced IL-6 messenger RNA expression in elutriated monocytes and IL-6 secretion in the supernatant. TGF beta did not induce IL-6. In contrast, TGF beta added to the culture inhibited, in a dose-dependent manner, the induction of IL-6 by IL-1 at the level of messenger RNA and bioactivity. These results show that IL-1 beta is able to stimulate IL-6 production by monocytes, TGF beta, by inhibiting this effect, may play an important role in regulating the IL-1-mediated components of the inflammatory response.

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