scholarly journals Analysis of activin/TGFB-signaling modulators within the normal and dysfunctional adult human testis reveals evidence of altered signaling capacity in a subset of seminomas

Reproduction ◽  
2009 ◽  
Vol 138 (5) ◽  
pp. 801-811 ◽  
Author(s):  
Vinali L Dias ◽  
Ewa Rajpert-De Meyts ◽  
Robert McLachlan ◽  
Kate Lakoski Loveland
Keyword(s):  
Growth Factor ◽  
Cellular Localization ◽  
Transforming Growth Factor ◽  
Male Gamete ◽  
Transforming Growth Factor Β ◽  
Human Testis ◽  
Adult Human ◽  
Normal Men ◽  
And Function ◽  
Tgfb Signaling

Activin is a pleiotropic growth factor belonging to the transforming growth factor-β (TGFB) superfamily of signaling molecules. Regulated activin signaling is known to influence several steps in rodent male gamete differentiation. TGFB ligand isoforms, TGFB1–B3, also influence germ cell survival in the rodent testis at the onset of spermatogenesis and around the time of puberty. Given the importance of regulated activin and TGFB signaling in testis development and function, we sought to investigate the cellular production sites of activin/TGFB-signaling modulators in normal and dysfunctional adult human testes samples. Signaling transducers phosphorylated SMAD2/3, and signaling modulators SMAD6, MAN-1, inhibin α (INHA), and β-glycan were detected in Bouins fixed, paraffin–embedded adult human testis sections using immunohistochemistry. Additional samples examined were from testicular cancer patients and from normal men subjected to gonadotropin suppression with androgen-based contraceptives. Our findings identify distinct differences between normal and gonadotropin-deprived human testis in the expression and cellular localization of activin/TGFB-signaling modulators. The presence of a nuclear phosphorylated SMAD2/3 signal in all analyzed seminoma specimens indicated active activin/TGFB signaling. Moreover, a subset of seminoma specimens exhibited selective enhanced expression of β-glycan (4 out of 28 seminoma tumors), INHA (6 out of 28), and MAN-1 (6 out of 28), highlighting potential functional differences between individual tumors in their capacity to regulate activin/TGFB signaling. Within the heterogenous nonseminomas, expression of signaling modulators was variable and reflected the degree of somatic differentiation. Thus, synthesis of activin and TGFB-signaling modulators may be affected by spermatogenic disruption and altered hormone levels in the testis.

scholarly journals Expression and Function of Transforming Growth Factor β in Melioidosis

2012 ◽  
Vol 80 (5) ◽  
pp. 1853-1857 ◽  
Author(s):  
Tassili A. F. Weehuizen ◽  
Catharina W. Wieland ◽  
Gerritje J. W. van der Windt ◽  
Jan-Willem Duitman ◽  
Louis Boon ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Organ Injury ◽  
Antibody Treatment ◽  
Content Type ◽  
Smad2 Phosphorylation ◽  
Distant Organ ◽  
Proinflammatory Role ◽  
And Function

ABSTRACTMelioidosis, caused by the Gram-negative bacteriumBurkholderia pseudomallei, is an important cause of community-acquired sepsis in Southeast Asia and northern Australia. An important controller of the immune system is the pleiotropic cytokine transforming growth factor β (TGF-β), of which Smad2 and Smad3 are the major signal transducers. In this study, we aimed to characterize TGF-β expression and function in experimental melioidosis. TGF-β expression was determined in 33 patients with culture-proven infection withB. pseudomalleiand 30 healthy controls. We found that plasma TGF-β concentrations were strongly elevated during melioidosis. In line with this finding, TGF-β expression in C57BL/6 mice intranasally inoculated withB. pseudomalleiwas enhanced as well. To assess the role of TGF-β, we inhibited TGF-β using a selective murine TGF-β antibody. Treatment of mice with anti-TGF-β antibody resulted in decreased lung Smad2 phosphorylation. TGF-β blockade appeared to be protective: mice treated with anti-TGF-β antibody and subsequently infected withB. pseudomalleishowed diminished bacterial loads. Moreover, less distant organ injury was observed in anti-TGF-β treated mice as shown by reduced blood urea nitrogen (BUN) and aspartate transaminase (AST) values. However, anti-TGF-β treatment did not have an effect on survival. In conclusion, TGF-β is upregulated duringB. pseudomalleiinfection and plays a limited but proinflammatory role during experimental melioidosis.

Transforming Growth Factor-β 1 Inhibits Ovarian Androgen Production: Gene Expression, Cellular Localization, Mechanisms(s), and Site(s) of Action*

Endocrinology ◽  
1990 ◽  
Vol 127 (6) ◽  
pp. 2804-2811 ◽  
Author(s):  
ELEUTERIO R. HERNANDEZ ◽  
ARYE HURWITZ ◽  
DONNA W. PAYNE ◽  
A. M. DHARMARAJAN ◽  
ANTHONY F. PURCHIO ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Cellular Localization ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β

scholarly journals SUN-552 Follistatin-Like 3 (FSTL3), a Transforming Growth Factor β (TGFβ) Ligand Inhibitor, Regulates Placental Development in Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Josef Huntington ◽  
Rachel Robertson ◽  
Gurtej K Dhoot ◽  
Imelda M McGonnell ◽  
Caroline Wheeler-Jones ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cellular Proliferation ◽  
Transforming Growth Factor ◽  
Expression Patterns ◽  
Transforming Growth Factor Β ◽  
Placental Development ◽  
Matrix Deposition ◽  
Smad2 Phosphorylation ◽  
Placental Efficiency ◽  
And Function

Abstract Follistatin-like 3 (FSTL3), a glycoprotein that inhibits transforming growth factor-β (TGFβ) ligands such as activin, is expressed highly in the placenta and other vascular tissues. In addition, FSTL3 is strongly induced in pre-eclamptic placenta. To test the hypothesis that FSTL3 function is required for capillary bed structure and function we studied the placenta in FSTL3 gene deleted mice (FSTL3 KO). We have previously shown that FSTL3 deletion produces striking defects in the placenta when compared to WT. Placental size increases significantly in comparison to WT, at 16.5 and 18.5 dpc, with concurrent reduction in placental efficiency at 18.5 dpc. Histological analyses reveal structural differences in placental junctional zones in FSTL3 KO placenta compared to WT. Morphometric analyses show that the labyrinth area compared to the placenta area is significantly reduced in FSTL3 KO mice. We also found that activin-responsive FSTL3-synexpression genes are upregulated in FSTL3 KO placenta. Of these, EPHB4 protein is induced in the placenta along with its ligand EphrinB2. Here we show that FSTL3 deletion leads to endothelial cell expansion but reduction in blood vessel density along with increased extracellular matrix deposition. Further investigation of the placental phenotype revealed differential expression patterns of desmin and cytokeratin protein, reduced von Willebrand factor (VWF) and increased CD31 and VEGFR2 labelling within FSTL3 KO mice placental labyrinths. To identify mechanisms that might lead to the altered placental development in FSTL3 KO mice qPCR analyses were performed. Our results identified differences in the expression of crucial transcripts, such as Cdh5, Pgf, Fra1and Cited1, that are associated with the regulation of vascular biology. Additionally, we find increased Histone3 and SMAD2 phosphorylation in FSTL3 KO placenta indicating increased proliferation and activin signalling, respectively. These findings suggest that the balance between cellular proliferation and differentiation might be altered in the absence of FSTL3. Thus, we conclude that FSTL3 function, at least partly through the inhibition of activin action, is necessary for normal placental circulation and development.

scholarly journals Generation and function of immunosuppressive human and murine CD8+ T cells by transforming growth factor-β and retinoic acid

Immunology ◽  
2011 ◽  
Vol 134 (1) ◽  
pp. 82-92 ◽  
Author(s):  
Diana Fleissner ◽  
Annika Frede ◽  
Markus Knott ◽  
Torben Knuschke ◽  
Robert Geffers ◽  
...  
Keyword(s):  
T Cells ◽  
Retinoic Acid ◽  
Growth Factor ◽  
Cd8 T Cells ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
And Function

Myofibroblasts. I. Paracrine cells important in health and disease

1999 ◽  
Vol 277 (1) ◽  
pp. C1-C19 ◽  
Author(s):  
D. W. Powell ◽  
R. C. Mifflin ◽  
J. D. Valentich ◽  
S. E. Crowe ◽  
J. I. Saada ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Proliferation And Differentiation ◽  
Health And Disease ◽  
Injury And Repair ◽  
And Function ◽  
Parenchymal Cells

Myofibroblasts are a unique group of smooth-muscle-like fibroblasts that have a similar appearance and function regardless of their tissue of residence. Through the secretion of inflammatory and anti-inflammatory cytokines, chemokines, growth factors, both lipid and gaseous inflammatory mediators, as well as extracellular matrix proteins and proteases, they play an important role in organogenesis and oncogenesis, inflammation, repair, and fibrosis in most organs and tissues. Platelet-derived growth factor (PDGF) and stem cell factor are two secreted proteins responsible for differentiating myofibroblasts from embryological stem cells. These and other growth factors cause proliferation of myofibroblasts, and myofibroblast secretion of extracellular matrix (ECM) molecules and various cytokines and growth factors causes mobility, proliferation, and differentiation of epithelial or parenchymal cells. Repeated cycles of injury and repair lead to organ or tissue fibrosis through secretion of ECM by the myofibroblasts. Transforming growth factor-β and the PDGF family of growth factors are the key factors in the fibrotic response. Because of their ubiquitous presence in all tissues, myofibroblasts play important roles in various organ diseases and perhaps in multisystem diseases as well.

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